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World J Clin Cases. Apr 16, 2015; 3(4): 345-352
Published online Apr 16, 2015. doi: 10.12998/wjcc.v3.i4.345
Atherosclerosis and the role of immune cells
Fulya Ilhan, Department of Immunology, Faculty of Medicine, University of Firat, 23200 Elazıg, Turkey
Sevgi Tas Kalkanli, Department of Immunology, Faculty of Medicine, University of Dicle, 21280 Diyarbakir, Turkey
Author contributions: İlhan F and Kalkanli ST contributed equally to writing the manuscript; both authors revised the article and approved the final version.
Conflict-of-interest: There is no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Fulya Ilhan, MD, PhD, Professor, Department of Immunology, Faculty of Medicine, University of Firat, 23200 Elazıg, Turkey. fulhan23@yahoo.com
Telephone: +90-424-2122960 Fax: +90-424-2379138
Received: May 13, 2014
Peer-review started: May 13, 2014
First decision: June 6, 2014
Revised: December 1, 2014
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: April 16, 2015

Abstract

Atherosclerosis is a chronic inflammatory disease arising from lipids, specifically low-density lipoproteins, and leukocytes. Following the activation of endothelium with the expression of adhesion molecules and monocytes, inflammatory cytokines from macrophages, and plasmacytoid dendritic cells, high levels of interferon (IFN)-α and β are generated upon the activation of toll-like receptor-9, and T-cells, especially the ones with Th1 profile, produce pro-inflammatory mediators such as IFN-γ and upregulate macrophages to adhere to the endothelium and migrate into the intima. This review presents an exhaustive account for the role of immune cells in the atherosclerosis.

Key Words: Atherosclerosis, Inflammatory cytokines, Pro-inflammatory mediators, Immune cells, Adhesion molecules

Core tip: Activated endothelium to adhere to the endothelium and move into the intima with the expression of adhesion molecules appears to be an early event in atherosclerosis, which allows mononuclear leukocytes such as monocytes and T-cells. This inflammatory mechanism must be explained before determining a new therapy.



INTRODUCTION

Atherosclerosis is one of the leading causes of morbidity and mortality arising from coronary artery disease, stroke, and peripheral vascular disease. The pathophysiology of atherosclerosis is best characterized with hyperlipidemia and inflammation[1,2].

For a long time after recognition, atherosclerosis was associated with passive lipid accumulation in the vessel wall. Nowadays we know that atherosclerosis is a chronic inflammatory disorder caused by lipids, particularly low-density lipoproteins (LDLs), and leukocytes[3]. Atherosclerosis is likely to be initiated by the activation of endothelium with the expression of adhesion molecules, and this in turn enables the adhesion of mononuclear leukocytes, such as monocytes and T-cells, to the endothelium and also their transmigration into the intima. At this point, the lesions may be present with rare cells such as dendritic cells (DCs), few neutrophils and B-cells, and also with smooth muscle cells (SMC), which transform phenotype into synthetic SMC and move into the intima from the media[4].

Polymorphonuclears (PMNs) are recruited and adhered to the endothelium upon the subsequent expression of adhesion molecules, such as E-selectin, P-selectin and intercellular adhesion molecule 1 (ICAM-1)[5]. The endothelial cell expression of selectins and vascular cell adhesion molecule 1 (VCAM-1) is further increased by pro-inflammatory cytokines and mmLDL, and this facilitates the infiltration of the monocytes into the intima[6]. As a result of intimal lipid accumulation, disturbed blood flow, low shear stress, and other stimuli, the transition of monocytes, which are major precursors of macrophages, through the endothelium is allowed by endothelial cells[3]. Endothelial cells and SMCs are triggered by oxidized LDL (OxLDL), and this leads to the secretion of monocytic maturation factors such as monocyte-colony stimulating factor (M-CSF). Monocytes are transformed to macrophages and phagocytose modified lipoproteins, mainly due to the scavenger receptors AI and CD36[7], and then become foam cells[8]. Macrophages may be activated by PMNs following the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-8, and interferon (IFN)-γ. In addition, the release of myeloperoxidase from granules can stimulate the formation of reactive oxygen species (ROS), as well as the secretion of other pro-inflammatory cytokines, including TNF-α, IL-1, IL-6, IL-8 and granulocyte macrophage colony stimulating factor (GM-CSF) from macrophages. In response, ROS transform the extravasated LDL into OxLDL, consequently forming the foam cell development[9].

Monocyte recruitment and the size of atherosclerotic lesion are bound to decrease if a failure is experienced in adhesion molecules, such as P-selectin, ICAM-1 and VCAM-1, or their interactions with their respective ligands are constrained[10,11].

MONOCYTES AND MACROPHAGES

After the migration from the circulation into the intima of the arterial wall, monocytes are converted to macrophages and DCs. These cells then transform into foam cells by taking up modified lipoproteins[12]. There are three major monocyte subsets in humans[13,14]: the classical CD14++CD16- subset is similar to the mouse Ly6C high inflammatory subset and also presents a high expression of CCR2, and the non-classical CD14+CD16++ monocytes are considered to match the Ly6C- cells in mice, which express high levels of CX3CR1 and CCR5 but low levels of CCR2[15]. The third subset, however, is known as the intermediate CD14++CD16+CCR2+ subset[16]. Of these, the classical subset includes nearly 90% of the monocytes circulating in humans[17]. The patients with coronary artery disease present with increased amount of pro-inflammatory CD14+CD16+ monocytes and serum TNF-α levels[18], and this monocyte subset is in negative correlation with fibrous cap thickness[19].

After chemokinesis, monocytes adhere to and spin on endothelial cells by interacting with E- and P-selectins[20,21]. Lipoprotein-binding proteoglycans are secreted by monocytes in the intima, leading to enhanced accumulation of modified LDL, which carries on inflammation[22,23].

Tissue damage and repair are closely linked to monocytes, and a discrepancy to occur in these processes may have critical results for plaque formation and stability. Importantly, monocytes consist of dissimilar subsets along with different cell surface markers and functional features, and this diversity of components may be associated with the angiogenic processes in atherosclerosis[24].

The formation of atherosclerotic lesions is heavily dependent on the transformation of monocytes into macrophages; for instance, M-CSF-knockout mice show resistance to the development of atherosclerosis[25].

Every phase of the course of disease includes abundant amounts of monocyte-derived macrophages[12], and these cells an important role in lipid accumulation and advancement of atherosclerosis[24]. Also, their crucial role in atherogenesis has been proven by the reduction of lesion formation in monocyte-deficient apolipoprotein E (ApoE) knockout mice and LDL receptor knockout mice[26,27].

The polarization of macrophages towards a specific phenotype has been reported to be positively affected by lipids, growth factors, and cytokines; the M1 macrophages that are classified by means of classical methods may result in plaque vulnerability, whereas the M2 macrophages which are activated by alternative methods may increase plaque stability[28]. The phenotypes of M1/M2 macrophages can be exchanged depending on the conditions of their microenvironment[29].

Many macrophages and dendritic-like cells are known to have membrane-bound lipid droplets in the cytoplasm even at very early phases of atherogenesis. As they comprise lipid deposits, these cells are called ‘‘foam cells’’ and their course of development is initiated when apolipoprotein B-containing lipoproteins (apoB-LPs) are absorbed and processed by phagocytes[21]. While producing matrix metalloproteinases with regards to plaque rupture, macrophages can be primed by oxLDL to develop a foam cell macrophage which bears the characteristics of M1 and M2 activation[28]. Inflammatory cytokines and chemokines that promote inflammation and contribute to the regulation of monocyte/T cell infiltration are generated by macrophages/foam cells[30-33]. With the macrophages in the atherosclerotic plaque, it is possible to generate a wide range of proinflammatory cytokines such as IL-1, IL-6, IL-12, IL-15, IL-18, TNF family members, and MIF, as well as anti-inflammatory cytokines like IL-10 and transforming growth factor beta family members[34,35]. Additionally, IFNγ may trigger the macrophages to produce ROS and neopterin. It has been reported that neopterin levels increased in acute coronary syndrome and neopterin may be useful for the assessment of inflammation related to atherosclerosis[36].

Being the most abundant cell type in atherosclerotic plaques, macrophages have a strong effect on plaque development and progression due to its overwhelming influence on intra-plaque cholesterol homeostasis, inflammation, necrotic core initiation, and extracellular matrix degradation[37].

Toll-like receptors (TLRs) represent the most comprehensively studied and described type of pattern recognition receptors. TLRs are characterized as type 1 transmembrane proteins involving an ectodomain with leucine-rich patterns that are needed to recognize pathogen associated molecular patterns, a transmembrane region, which determines the locations of the cells, and an intracellular toll interleukin 1 receptor region required for downstream signaling. Up to now, a minimum of 13 TLRs have been described, and each of them present with a degree of specificity for a number of endogenous and exogenous ligands[38]. Expression of TLRs is performed by a number of various cells, such as leukocytes, DCs, and T and B lymphocytes[39]. Atheroma development can be directly influenced by TLRs since the lipid uptake is promoted when the stimulation of macrophages is conducted with TLR2, TLR4 and TLR9 ligands[40,41]. According to recent studies on ApoE-/- mice, even small amounts of TLR4 and TLR2 have positive effects on the deposition of early-stage intimal foam cells in some regions in the aorta which are sensitive to lesion development[42]. The macropinocytosis of lipids in differentiated macrophages can be stimulated by TLR4[43]. Increased expression of scavenger receptors induced by TLR3, TLR4 and TLR9 can be used as a mediator for increased lipid absorption[39,44]. These receptors and their ligands may also interrupt the cholesterol efflux mechanisms, which may have a contributory role in the development of foam cells[28].

THE DENDRITIC CELLS

Dendritic cells, which are antigen-presenting cells (APCs), exhibit a variety of antigens to T cells in addition to initiating and sustaining immune responses as well as inhibiting the activation of T cells. The capacity of DCs in the activation or inhibition of T cells relies on its cytokine production profile and expression of cell surface co-stimulatory molecules. DCs are transformed by activated innate immune receptors, such as the TLR, into APCs that activate T effector cells, whereas, immunological tolerance is produced by antigen presentation which develops when TLR activation is not present. Therefore, DCs play a critical role as a connector between innate and adaptive immune responses[45].

DC has a heterogeneous population with four major categories: conventional DCs (cDCs), plasmacytoid DCs (pDCs), monocyte-derived DCs, and Langerhans cells[46]. Monocytes or DC precursors, which are present in the bone marrow, constitute the two sources of DCs.

Monocytes are completely transformed into monocyte-derived DCs in inflammation and as a reaction to growth factors like GM-CSF or TLR4 ligands. The capacity of presenting antigens along with the ability to cross-present antigens belongs to the DCs that originate from monocytes[37]. DCs are capable of generating a wide range of anti-inflammatory and proinflammatory cytokines. As an example, some proinflammatory cytokines, such as TNF, IL-6, and IL-12, which have been proven to contribute to the atherosclerosis can be generated by TLR binding[47-49]. However, TLR binding may also generate IL-10, which is known as an atheroprotective cytokine[50].

The DCs in mice are best known for their expression of CD11c and they present with healthy mouse aortas, predominantly in the adventitia[51]. In mice, the amount of mRNA expression of CD11c is higher in the sites of the aortic arch susceptible to atherosclerosis, compared to the sites that are resistant to atherosclerosis. Contrary to healthy vessels, most of the DCs in atherosclerotic aortas are localized in the intima[52].

The deposition of CD11c+ DCs at the vascular regions prone to atherosclerosis is associated with the increase in the expression of VCAM-1[53]. Mature DCs are more abundant in advanced lesions. High level of expression of human leukocyte antigen (HLA)-DR and interactions with T cells are mostly observed in the sites of the plaque that are predisposed to rupture[54]. The deposition process of the dendritic cells in the intima may be interrupted if the fractalkine receptor CX3CR1 in the aorta is impaired, and this may be an indication that these cells may be transformed from Ly-6Clo monocytes which are known to induce high levels of CX3CR1[55]. OxLDL, in line with the elevation in the production of T cells, functions as an antigen upregulator for the DC expression of HLA-DR and its co-stimulatory molecules[56]. DCs carry out the expression of scavenger receptors (LOX-1, CD36 and CD205) which facilitate their uptake of oxLDL activating the NFκB pathway, and evolution to DCs with a pro-inflammatory cytokine profile[57]. Once DCs are activated by oxLDL in the plaque, they move to secondary lymphoid organs and initiate the clonal proliferation of the T cells that are specific to oxLDL[28].

Following TLR9 activation, it is a common event for pDCs to produce high amounts of IFNα and β, and TLR9 has been reported to contribute to atherosclerosis by promoting macrophage recruitment[58]. The recruitment of monocytes, memory T cells, and DCs to the region of inflammation is reportedly influenced by the CCL2 secreted by DCs[59].

DCs, as prominent mediators of immune responses, may also act as the regulators of innate or adaptive immunity against the potential antigens that are engaged in atherosclerosis[60]. In brief, the roles of dendritic cells in atherosclerosis can be summarized as the induction of chemokines and cytokines, presentation of antigens, and lipid absorption that might trigger inflammation or promote tolerance[37].

T CELLS

The role of adaptive immunity in atherosclerosis was verified by the presence of antibodies and oxLDL-specific T cells along with the accumulation of oligoclonal T cells in lesions[6,61]. T cells are targeted to the vessel wall in line with macrophages, but to a lesser extent. Activation of T cells in the arterial wall is a reaction to antigens, and after this activation, the T cells initiate the production of pro-inflammatory mediators, by which the inflammatory response is intensified and thus the disease development is worsened[62]. Moreover, most of the pathogenic T cells in atherosclerosis have the characteristics of Th1 since they generate pro-inflammatory cytokines such as IFN-γ and perform the activation of macrophages[63,64]. The reactions mediated by Th1 have harmful effects on the development of atherosclerosis. Vascular smooth muscle cells are recruited by IFN-γ to inhibit the synthesis of collagen, and this leads to harmful effects for the protective thick fibrous cap of the plaque. Also, the activation of monocytes/macrophages and dendritic cells by IFN-γ results in the continuation of the pathogenic Th1 response[30].

Previous studies report that the removal of IFNγ or its receptors leads to a reduction in atherosclerosis, whereas the injection of recombinant IFNγ results in a growth in the size of the lesions[65-67]. The detection of Th2 cells in the atherosclerotic lesions is a rare occurrence. The cytokines produced by Th2 cells include IL-4, IL-5, IL-9, and IL-13. Th2 cells also have contributory effects on the production of antibodies by B cells. As the production of IFN-γ is decreased by these cells, the responses caused by Th2 were thought to be the antagonists of proatherogenic Th1 effects, hence rendering atheroprotection. Nevertheless, how atherosclerotic progress is affected by Th2 pathway has yet to be proven and the role Th2 pathway relies not only on the phase and location of the lesion but also on the method of experimentation to be used[62]. According to some studies on animals, both Th1 and Th2 responses are involved in the progression of atherosclerosis, and lesion formation is started primarily by Th1 activation through a switch towards a proatherogenic response by Th2 in the chronic stage of plaque formation[68]. The expansion and cytokine induction of highly activated effector T cells can also be inhibited by another T cell called TCRγδ+ CD4- CD8-, and this cell may need to be further analyzed since it is likely to have antiatherogenic characteristics[69,70]. The regulatory T cells (Tregs) have critical roles in the inhibition and suppression of inflammation and also in the regulation of adaptive immune responses. Moreover, these cells can induce tolerance by inhibiting the effector CD4+ and CD8+ T cells[71,72].

IL-10 has been reported to inhibit atherosclerosis, and thus the athero-protective effects of regulatory T cells may be improved when they generate IL-10[73,74]. Studies also report that IL-10 has a protective function in the development and stability of atherosclerotic lesions[72,73].

Th17 lymphocytes represent another T helper subset associated with inflammation, and this subset does not share the same lineage with Th1 and Th2[75]. IL-17 has been demonstrated to have protective and pathogenic effects in a number of autoimmune diseases[76,77].

The main cytokines expressed by Th17 cells include IL-17A and IL-17F along with IL-21 and IL-22. The role of Th17 is still debatable despite the detection of Th17 cells in the atherosclerotic lesions in mice and humans, because both atherogenic and atheroprotective effects have been attributed to these cells[78-80]. IL-17 is also considered to enhance plaque stability since elevated IL-17 induction in human lesions results in a decrease in the number of macrophages, an increase in SMC deposit, and a phenotype with a more fibrotic profile[81].

Proatherogenic profile of IL-17 has been shown previously by many studies[82-85]. In these studies, the evidence for the proatherogenic effect of IL-17 is attributed to the fact that both IL-17 and IFN-γ are expressed by the CD4+ T cells that are separated from atherosclerotic coronary vessels[86].

CD8+ T cells are detected in both murine and human plaques[87,88]. The number of CD8+ T cells is low in the early stages of lesions; however, these cells seem to be the dominant T cell type in the advanced stages of human lesions[88]. CD8+ T cells may have a proatherogenic function since the lesion size was increased and also the recruitment of these cells to the lesion site was promoted when the responses of these cells were stimulated with a CD137 agonist[89].

B CELLS

The responses produced by the Th2 cell have important roles in the activation of B cells, the differentiation of plasma cells, and the production of antibodies that are unique to antigens. B cells are evident in atherosclerotic lesions, but their population is smaller than that of T cells[90]. However, the role of B cells in atherosclerosis remains controversial as two recent studies have reported that the atherosclerotic progression in mice is inhibited when B cells are blocked by the use of an antibody against CD20[91,92]. The evidence that some types of IgM and IgG have atheroprotective effects may suggest that B cells have the ability to protect against atherosclerosis. Moreover, plaques have been detected with both IgM and IgG at all phases of lesion progression[93]. Anti-oxLDL IgM antibodies have been proven to provide protection against atherosclerosis, probably because they achieve oxLDL binding and thus suppress oxLDL absorption by using macrophages and avoid the development of foam cells[94,95]. On the other hand, to what extent the oxLDL-specific IgG is effective remains a controversial issue because both beneficial and inverse effects have been reported in epidemiological studies[96]. OxLDL-specific antibody IgG titers are associated with atherosclerosis[94,97,98], whereas oxLDL-specific IgM titers are related to atheroprotection[99,100]. Nonetheless, the B cell subsets and their roles in atherosclerosis need to be further analyzed[37].

CONCLUSION

Atherosclerosis is a multiphase process which is characterized with the activation of endothelial cells with the expression of adhesion molecules and monocytes/macrophages, and the transmigration of DCs, T cells and some B-cells into the intima, and also the transfer of modulated types of LDL to matrix components. Monocytes/macrophages are highly abundant and differentiate into foam cells which are rich in modulated LDL.

According to clinical and experimental data, the atherogenic process involves the cells of both the innate and the adaptive immune system, and these cells generate diverse cytokines that may have both pro and anti-inflammatory functions[101-103]. To immunomodulate the atherosclerosis is the primary aim of some clinical studies. Among these, the experimental studies with anti-LDL antibodies and vaccination studies with LDLs are under way[1,104]. Oral administration of oxidized LDLs is reported to be effective on the inhibition of atherosclerosis and production of Tregs in peripheral lymphoid tissues[105]. The functions of immune and inflammatory modulators in the formation and development of atherosclerosis have been better analyzed in recent years and thus provided a deeper insight into these mechanisms. Accordingly, more and more advanced techniques in the diagnosis and prognosis of atherosclerosis, along with new treatment procedures for inflammatory and immune factors, have been developed[106]. However, there is still much to learn about immune cells and their mechanisms affecting atherosclerosis. We believe that further studies investigating immune cells and their mechanisms will help to shed light on atherosclerosis.

Footnotes

P- Reviewer: Nemcsik J, Wei L S- Editor: Song XX L- Editor: A E- Editor: Lu YJ

References
1.  Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317-325.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2419]  [Cited by in F6Publishing: 2561]  [Article Influence: 197.0]  [Reference Citation Analysis (0)]
2.  Rader DJ, Daugherty A. Translating molecular discoveries into new therapies for atherosclerosis. Nature. 2008;451:904-913.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 363]  [Cited by in F6Publishing: 361]  [Article Influence: 22.6]  [Reference Citation Analysis (0)]
3.  Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339:161-166.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 694]  [Cited by in F6Publishing: 744]  [Article Influence: 67.6]  [Reference Citation Analysis (0)]
4.  Frostegård J. Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013;11:117.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 496]  [Cited by in F6Publishing: 578]  [Article Influence: 52.5]  [Reference Citation Analysis (0)]
5.  Collins RG, Velji R, Guevara NV, Hicks MJ, Chan L, Beaudet AL. P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J Exp Med. 2000;191:189-194.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 371]  [Cited by in F6Publishing: 360]  [Article Influence: 15.0]  [Reference Citation Analysis (0)]
6.  Hansson GK, Robertson AK, Söderberg-Nauclér C. Inflammation and atherosclerosis. Annu Rev Pathol. 2006;1:297-329.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 713]  [Cited by in F6Publishing: 731]  [Article Influence: 43.0]  [Reference Citation Analysis (0)]
7.  Hazen SL. Oxidized phospholipids as endogenous pattern recognition ligands in innate immunity. J Biol Chem. 2008;283:15527-15531.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 139]  [Cited by in F6Publishing: 139]  [Article Influence: 8.7]  [Reference Citation Analysis (0)]
8.  Sanders M. Molecular and cellular concepts in atherosclerosis. Pharmacol Ther. 1994;61:109-153.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 44]  [Cited by in F6Publishing: 45]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
9.  Tavakoli S, Asmis R. Reactive oxygen species and thiol redox signaling in the macrophage biology of atherosclerosis. Antioxid Redox Signal. 2012;17:1785-1795.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 57]  [Cited by in F6Publishing: 60]  [Article Influence: 5.0]  [Reference Citation Analysis (0)]
10.  Nageh MF, Sandberg ET, Marotti KR, Lin AH, Melchior EP, Bullard DC, Beaudet AL. Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 1997;17:1517-1520.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 173]  [Cited by in F6Publishing: 172]  [Article Influence: 6.4]  [Reference Citation Analysis (0)]
11.  Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos JC, Connelly PW, Milstone DS. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest. 2001;107:1255-1262.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 841]  [Cited by in F6Publishing: 855]  [Article Influence: 37.2]  [Reference Citation Analysis (0)]
12.  Profumo E, Buttari B, Saso L, Capoano R, Salvati B, Riganò R. T lymphocyte autoreactivity in inflammatory mechanisms regulating atherosclerosis. ScientificWorldJournal. 2012;2012:157534.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 18]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
13.  Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, Leenen PJ, Liu YJ, MacPherson G, Randolph GJ. Nomenclature of monocytes and dendritic cells in blood. Blood. 2010;116:e74-e80.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1589]  [Cited by in F6Publishing: 1646]  [Article Influence: 117.6]  [Reference Citation Analysis (0)]
14.  Shantsila E, Lip GY. Monocyte diversity in myocardial infarction. J Am Coll Cardiol. 2009;54:139-142.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 22]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
15.  Weber C, Belge KU, von Hundelshausen P, Draude G, Steppich B, Mack M, Frankenberger M, Weber KS, Ziegler-Heitbrock HW. Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol. 2000;67:699-704.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Zawada AM, Rogacev KS, Rotter B, Winter P, Marell RR, Fliser D, Heine GH. SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood. 2011;118:e50-e61.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 350]  [Cited by in F6Publishing: 389]  [Article Influence: 29.9]  [Reference Citation Analysis (0)]
17.  Gautier EL, Jakubzick C, Randolph GJ. Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:1412-1418.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 157]  [Cited by in F6Publishing: 162]  [Article Influence: 10.8]  [Reference Citation Analysis (0)]
18.  Schlitt A, Heine GH, Blankenberg S, Espinola-Klein C, Dopheide JF, Bickel C, Lackner KJ, Iz M, Meyer J, Darius H. CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels. Thromb Haemost. 2004;92:419-424.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Imanishi T, Ikejima H, Tsujioka H, Kuroi A, Ishibashi K, Komukai K, Tanimoto T, Ino Y, Takeshita T, Akasaka T. Association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris. Atherosclerosis. 2010;212:628-635.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 63]  [Cited by in F6Publishing: 63]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
20.  Mestas J, Ley K. Monocyte-endothelial cell interactions in the development of atherosclerosis. Trends Cardiovasc Med. 2008;18:228-232.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 367]  [Cited by in F6Publishing: 385]  [Article Influence: 25.7]  [Reference Citation Analysis (0)]
21.  Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145:341-355.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1939]  [Cited by in F6Publishing: 1852]  [Article Influence: 142.5]  [Reference Citation Analysis (0)]
22.  Williams KJ, Tabas I. The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol. 1995;15:551-561.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 958]  [Cited by in F6Publishing: 922]  [Article Influence: 31.8]  [Reference Citation Analysis (0)]
23.  Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol. 2010;10:36-46.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 778]  [Cited by in F6Publishing: 806]  [Article Influence: 53.7]  [Reference Citation Analysis (0)]
24.  Jaipersad AS, Lip GY, Silverman S, Shantsila E. The role of monocytes in angiogenesis and atherosclerosis. J Am Coll Cardiol. 2014;63:1-11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 243]  [Cited by in F6Publishing: 278]  [Article Influence: 25.3]  [Reference Citation Analysis (0)]
25.  Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci USA. 1995;92:8264-8268.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  de Villiers WJ, Smith JD, Miyata M, Dansky HM, Darley E, Gordon S. Macrophage phenotype in mice deficient in both macrophage-colony-stimulating factor (op) and apolipoprotein E. Arterioscler Thromb Vasc Biol. 1998;18:631-640.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 56]  [Cited by in F6Publishing: 60]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
27.  Rajavashisth T, Qiao JH, Tripathi S, Tripathi J, Mishra N, Hua M, Wang XP, Loussararian A, Clinton S, Libby P. Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice. J Clin Invest. 1998;101:2702-2710.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 190]  [Cited by in F6Publishing: 191]  [Article Influence: 7.3]  [Reference Citation Analysis (0)]
28.  Seneviratne AN, Sivagurunathan B, Monaco C. Toll-like receptors and macrophage activation in atherosclerosis. Clin Chim Acta. 2012;413:3-14.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 67]  [Cited by in F6Publishing: 66]  [Article Influence: 5.1]  [Reference Citation Analysis (0)]
29.  Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi BS, Ruhrberg C, Cantley LG. Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol. 2011;22:317-326.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 593]  [Cited by in F6Publishing: 636]  [Article Influence: 48.9]  [Reference Citation Analysis (0)]
30.  Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006;86:515-581.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1139]  [Cited by in F6Publishing: 1175]  [Article Influence: 65.3]  [Reference Citation Analysis (0)]
31.  Gui T, Shimokado A, Sun Y, Akasaka T, Muragaki Y. Diverse roles of macrophages in atherosclerosis: from inflammatory biology to biomarker discovery. Mediators Inflamm. 2012;2012:693083.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 104]  [Cited by in F6Publishing: 129]  [Article Influence: 10.8]  [Reference Citation Analysis (0)]
32.  Wolfs IM, Donners MM, de Winther MP. Differentiation factors and cytokines in the atherosclerotic plaque micro-environment as a trigger for macrophage polarisation. Thromb Haemost. 2011;106:763-771.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 136]  [Cited by in F6Publishing: 144]  [Article Influence: 11.1]  [Reference Citation Analysis (0)]
33.  Koenen RR, Weber C. Chemokines: established and novel targets in atherosclerosis. EMBO Mol Med. 2011;3:713-725.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 76]  [Cited by in F6Publishing: 79]  [Article Influence: 6.1]  [Reference Citation Analysis (0)]
34.  Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol. 2009;27:165-197.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 994]  [Cited by in F6Publishing: 1038]  [Article Influence: 69.2]  [Reference Citation Analysis (0)]
35.  de Jager SC, Bermúdez B, Bot I, Koenen RR, Bot M, Kavelaars A, de Waard V, Heijnen CJ, Muriana FJ, Weber C. Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis. J Exp Med. 2011;208:217-225.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 134]  [Cited by in F6Publishing: 139]  [Article Influence: 10.7]  [Reference Citation Analysis (0)]
36.  Ilhan F, Akbulut H, Karaca I, Godekmerdan A, Ilkay E, Bulut V. Procalcitonin, c-reactive protein and neopterin levels in patients with coronary atherosclerosis. Acta Cardiol. 2005;60:361-365.  [PubMed]  [DOI]  [Cited in This Article: ]
37.  Legein B, Temmerman L, Biessen EA, Lutgens E. Inflammation and immune system interactions in atherosclerosis. Cell Mol Life Sci. 2013;70:3847-3869.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 204]  [Cited by in F6Publishing: 215]  [Article Influence: 19.5]  [Reference Citation Analysis (0)]
38.  O’Neill LA. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev. 2008;226:10-18.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 452]  [Cited by in F6Publishing: 458]  [Article Influence: 30.5]  [Reference Citation Analysis (0)]
39.  Cole JE, Georgiou E, Monaco C. The expression and functions of toll-like receptors in atherosclerosis. Mediators Inflamm. 2010;2010:393946.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 96]  [Cited by in F6Publishing: 115]  [Article Influence: 8.2]  [Reference Citation Analysis (0)]
40.  Lee JG, Lim EJ, Park DW, Lee SH, Kim JR, Baek SH. A combination of Lox-1 and Nox1 regulates TLR9-mediated foam cell formation. Cell Signal. 2008;20:2266-2275.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 63]  [Cited by in F6Publishing: 65]  [Article Influence: 4.1]  [Reference Citation Analysis (0)]
41.  Funk JL, Feingold KR, Moser AH, Grunfeld C. Lipopolysaccharide stimulation of RAW 264.7 macrophages induces lipid accumulation and foam cell formation. Atherosclerosis. 1993;98:67-82.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 134]  [Cited by in F6Publishing: 131]  [Article Influence: 4.2]  [Reference Citation Analysis (0)]
42.  Higashimori M, Tatro JB, Moore KJ, Mendelsohn ME, Galper JB, Beasley D. Role of toll-like receptor 4 in intimal foam cell accumulation in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2011;31:50-57.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 90]  [Cited by in F6Publishing: 97]  [Article Influence: 6.9]  [Reference Citation Analysis (0)]
43.  Choi SH, Harkewicz R, Lee JH, Boullier A, Almazan F, Li AC, Witztum JL, Bae YS, Miller YI. Lipoprotein accumulation in macrophages via toll-like receptor-4-dependent fluid phase uptake. Circ Res. 2009;104:1355-1363.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 169]  [Cited by in F6Publishing: 176]  [Article Influence: 11.7]  [Reference Citation Analysis (0)]
44.  Doyle SE, O’Connell RM, Miranda GA, Vaidya SA, Chow EK, Liu PT, Suzuki S, Suzuki N, Modlin RL, Yeh WC. Toll-like receptors induce a phagocytic gene program through p38. J Exp Med. 2004;199:81-90.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 299]  [Cited by in F6Publishing: 309]  [Article Influence: 14.7]  [Reference Citation Analysis (0)]
45.  Wigren M, Nilsson J, Kolbus D. Lymphocytes in atherosclerosis. Clin Chim Acta. 2012;413:1562-1568.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 42]  [Cited by in F6Publishing: 41]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
46.  Belz GT, Nutt SL. Transcriptional programming of the dendritic cell network. Nat Rev Immunol. 2012;12:101-113.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 194]  [Cited by in F6Publishing: 214]  [Article Influence: 17.8]  [Reference Citation Analysis (0)]
47.  Hermansson A, Ketelhuth DF, Strodthoff D, Wurm M, Hansson EM, Nicoletti A, Paulsson-Berne G, Hansson GK. Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis. J Exp Med. 2010;207:1081-1093.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 170]  [Cited by in F6Publishing: 175]  [Article Influence: 12.5]  [Reference Citation Analysis (0)]
48.  Schieffer B, Selle T, Hilfiker A, Hilfiker-Kleiner D, Grote K, Tietge UJ, Trautwein C, Luchtefeld M, Schmittkamp C, Heeneman S. Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis. Circulation. 2004;110:3493-3500.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 223]  [Cited by in F6Publishing: 225]  [Article Influence: 11.3]  [Reference Citation Analysis (0)]
49.  Zhang X, Niessner A, Nakajima T, Ma-Krupa W, Kopecky SL, Frye RL, Goronzy JJ, Weyand CM. Interleukin 12 induces T-cell recruitment into the atherosclerotic plaque. Circ Res. 2006;98:524-531.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 83]  [Cited by in F6Publishing: 85]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
50.  Samarasinghe R, Tailor P, Tamura T, Kaisho T, Akira S, Ozato K. Induction of an anti-inflammatory cytokine, IL-10, in dendritic cells after toll-like receptor signaling. J Interferon Cytokine Res. 2006;26:893-900.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 65]  [Cited by in F6Publishing: 65]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
51.  Moos MP, John N, Gräbner R, Nossmann S, Günther B, Vollandt R, Funk CD, Kaiser B, Habenicht AJ. The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005;25:2386-2391.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 162]  [Cited by in F6Publishing: 165]  [Article Influence: 8.7]  [Reference Citation Analysis (0)]
52.  Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D, Cybulsky MI. Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med. 2006;203:2073-2083.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 245]  [Cited by in F6Publishing: 251]  [Article Influence: 13.9]  [Reference Citation Analysis (0)]
53.  Yilmaz A, Lochno M, Traeg F, Cicha I, Reis C, Stumpf C, Raaz D, Anger T, Amannb K, Probst T. Emergence of dendritic cells in rupture prone region recent years, researchers have strong interests in HDL increasing strategies to prevent atherosclerosis of vulnerable carotid plaques. Atherosclerosis. 2004;176:101-110.  [PubMed]  [DOI]  [Cited in This Article: ]
54.  Liu P, Yu YR, Spencer JA, Johnson AE, Vallanat CT, Fong AM, Patterson C, Patel DD. CX3CR1 deficiency impairs dendritic cell accumulation in arterial intima and reduces atherosclerotic burden. Arterioscler Thromb Vasc Biol. 2008;28:243-250.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 125]  [Cited by in F6Publishing: 125]  [Article Influence: 7.4]  [Reference Citation Analysis (0)]
55.  Alderman CJ, Bunyard PR, Chain BM, Foreman JC, Leake DS, Katz DR. Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment? Cardiovasc Res. 2002;55:806-819.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 85]  [Cited by in F6Publishing: 87]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
56.  Nickel T, Schmauss D, Hanssen H, Sicic Z, Krebs B, Jankl S, Summo C, Fraunberger P, Walli AK, Pfeiler S. oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation. Atherosclerosis. 2009;205:442-450.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 74]  [Cited by in F6Publishing: 83]  [Article Influence: 5.5]  [Reference Citation Analysis (0)]
57.  Goossens P, Gijbels MJ, Zernecke A, Eijgelaar W, Vergouwe MN, van der Made I, Vanderlocht J, Beckers L, Buurman WA, Daemen MJ. Myeloid type I interferon signaling promotes atherosclerosis by stimulating macrophage recruitment to lesions. Cell Metab. 2010;12:142-153.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 172]  [Cited by in F6Publishing: 171]  [Article Influence: 12.2]  [Reference Citation Analysis (0)]
58.  Huang DR, Wang J, Kivisakk P, Rollins BJ, Ransohoff RM. Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med. 2001;193:713-726.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 455]  [Cited by in F6Publishing: 484]  [Article Influence: 21.0]  [Reference Citation Analysis (0)]
59.  Mallat Z, Ait-Oufella H, Tedgui A. Regulatory T-cell immunity in atherosclerosis. Trends Cardiovasc Med. 2007;17:113-118.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 91]  [Cited by in F6Publishing: 79]  [Article Influence: 4.6]  [Reference Citation Analysis (0)]
60.  Hansson GK, Holm J, Jonasson L. Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol. 1989;135:169-175.  [PubMed]  [DOI]  [Cited in This Article: ]
61.  Paulsson G, Zhou X, Törnquist E, Hansson GK. Oligoclonal T cell expansions in atherosclerotic lesions of apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2000;20:10-17.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 142]  [Cited by in F6Publishing: 144]  [Article Influence: 6.0]  [Reference Citation Analysis (0)]
62.  Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent advances on the role of cytokines in atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31:969-979.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 385]  [Cited by in F6Publishing: 394]  [Article Influence: 30.3]  [Reference Citation Analysis (0)]
63.  George J, Schwartzenberg S, Medvedovsky D, Jonas M, Charach G, Afek A, Shamiss A. Regulatory T cells and IL-10 levels are reduced in patients with vulnerable coronary plaques. Atherosclerosis. 2012;222:519-523.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 64]  [Cited by in F6Publishing: 76]  [Article Influence: 6.3]  [Reference Citation Analysis (0)]
64.  Whitman SC, Ravisankar P, Daugherty A. IFN-gamma deficiency exerts gender-specific effects on atherogenesis in apolipoprotein E-/- mice. J Interferon Cytokine Res. 2002;22:661-670.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 136]  [Cited by in F6Publishing: 140]  [Article Influence: 6.4]  [Reference Citation Analysis (0)]
65.  Gupta S, Pablo AM, Jiang Xc, Wang N, Tall AR, Schindler C. IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest. 1997;99:2752-2761.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 684]  [Cited by in F6Publishing: 663]  [Article Influence: 24.6]  [Reference Citation Analysis (0)]
66.  Buono C, Come CE, Stavrakis G, Maguire GF, Connelly PW, Lichtman AH. Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse. Arterioscler Thromb Vasc Biol. 2003;23:454-460.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 211]  [Cited by in F6Publishing: 212]  [Article Influence: 10.1]  [Reference Citation Analysis (0)]
67.  Ketelhuth DF, Hansson GK. Cellular immunity, low-density lipoprotein and atherosclerosis: break of tolerance in the artery wall. Thromb Haemost. 2011;106:779-786.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 77]  [Cited by in F6Publishing: 83]  [Article Influence: 6.4]  [Reference Citation Analysis (0)]
68.  Davenport P, Tipping PG. The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice. Am J Pathol. 2003;163:1117-1125.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 330]  [Cited by in F6Publishing: 327]  [Article Influence: 15.6]  [Reference Citation Analysis (0)]
69.  Voelkl S, Gary R, Mackensen A. Characterization of the immunoregulatory function of human TCR-αβ+ CD4- CD8- double-negative T cells. Eur J Immunol. 2011;41:739-748.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 72]  [Cited by in F6Publishing: 79]  [Article Influence: 6.1]  [Reference Citation Analysis (0)]
70.  Jäger A, Kuchroo VK. Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation. Scand J Immunol. 2010;72:173-184.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 185]  [Cited by in F6Publishing: 193]  [Article Influence: 13.8]  [Reference Citation Analysis (0)]
71.  George J. Mechanisms of disease: the evolving role of regulatory T cells in atherosclerosis. Nat Clin Pract Cardiovasc Med. 2008;5:531-540.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 54]  [Cited by in F6Publishing: 59]  [Article Influence: 3.7]  [Reference Citation Analysis (0)]
72.  Mallat Z, Besnard S, Duriez M, Deleuze V, Emmanuel F, Bureau MF, Soubrier F, Esposito B, Duez H, Fievet C, Staels B, Duverger N, Scherman D, Tedgui A. Protective role of interleukin-10 in atherosclerosis. Circ Res. 1999;85:e17-e24.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 500]  [Cited by in F6Publishing: 509]  [Article Influence: 20.4]  [Reference Citation Analysis (0)]
73.  Caligiuri G, Rudling M, Ollivier V, Jacob MP, Michel JB, Hansson GK, Nicoletti A. Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med. 2003;9:10-17.  [PubMed]  [DOI]  [Cited in This Article: ]
74.  Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson S. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med. 2006;12:178-180.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 744]  [Cited by in F6Publishing: 784]  [Article Influence: 43.6]  [Reference Citation Analysis (0)]
75.  Miossec P. IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect. 2009;11:625-630.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 163]  [Cited by in F6Publishing: 172]  [Article Influence: 11.5]  [Reference Citation Analysis (0)]
76.  O’Connor W, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, Kolls JK, Flavell RA. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol. 2009;10:603-609.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 593]  [Cited by in F6Publishing: 614]  [Article Influence: 40.9]  [Reference Citation Analysis (0)]
77.  Zhou W, Dowell DR, Huckabee MM, Newcomb DC, Boswell MG, Goleniewska K, Lotz MT, Toki S, Yin H, Yao S. Prostaglandin I2 signaling drives Th17 differentiation and exacerbates experimental autoimmune encephalomyelitis. PLoS One. 2012;7:e33518.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 26]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
78.  Smith E, Prasad KM, Butcher M, Dobrian A, Kolls JK, Ley K, Galkina E. Blockade of interleukin-17A results in reduced atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2010;121:1746-1755.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 313]  [Cited by in F6Publishing: 321]  [Article Influence: 22.9]  [Reference Citation Analysis (0)]
79.  Erbel C, Dengler TJ, Wangler S, Lasitschka F, Bea F, Wambsganss N, Hakimi M, Böckler D, Katus HA, Gleissner CA. Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic Res Cardiol. 2011;106:125-134.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 126]  [Cited by in F6Publishing: 129]  [Article Influence: 9.2]  [Reference Citation Analysis (0)]
80.  Xie JJ, Wang J, Tang TT, Chen J, Gao XL, Yuan J, Zhou ZH, Liao MY, Yao R, Yu X. The Th17/Treg functional imbalance during atherogenesis in ApoE(-/-) mice. Cytokine. 2010;49:185-193.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 133]  [Cited by in F6Publishing: 129]  [Article Influence: 8.6]  [Reference Citation Analysis (0)]
81.  Lahoute C, Herbin O, Mallat Z, Tedgui A. Adaptive immunity in atherosclerosis: mechanisms and future therapeutic targets. Nat Rev Cardiol. 2011;8:348-358.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 166]  [Cited by in F6Publishing: 177]  [Article Influence: 13.6]  [Reference Citation Analysis (0)]
82.  van Es T, van Puijvelde GH, Ramos OH, Segers FM, Joosten LA, van den Berg WB, Michon IM, de Vos P, van Berkel TJ, Kuiper J. Attenuated atherosclerosis upon IL-17R signaling disruption in LDLr deficient mice. Biochem Biophys Res Commun. 2009;388:261-265.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 117]  [Cited by in F6Publishing: 125]  [Article Influence: 8.3]  [Reference Citation Analysis (0)]
83.  Erbel C, Chen L, Bea F, Wangler S, Celik S, Lasitschka F, Wang Y, Böckler D, Katus HA, Dengler TJ. Inhibition of IL-17A attenuates atherosclerotic lesion development in apoE-deficient mice. J Immunol. 2009;183:8167-8175.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 248]  [Cited by in F6Publishing: 261]  [Article Influence: 18.6]  [Reference Citation Analysis (0)]
84.  Gao Q, Jiang Y, Ma T, Zhu F, Gao F, Zhang P, Guo C, Wang Q, Wang X, Ma C. A critical function of Th17 proinflammatory cells in the development of atherosclerotic plaque in mice. J Immunol. 2010;185:5820-5827.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 166]  [Cited by in F6Publishing: 168]  [Article Influence: 12.0]  [Reference Citation Analysis (0)]
85.  Chen S, Shimada K, Zhang W, Huang G, Crother TR, Arditi M. IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae infection-accelerated atherosclerosis in mice. J Immunol. 2010;185:5619-5627.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 86]  [Cited by in F6Publishing: 90]  [Article Influence: 6.4]  [Reference Citation Analysis (0)]
86.  Eid RE, Rao DA, Zhou J, Lo SF, Ranjbaran H, Gallo A, Sokol SI, Pfau S, Pober JS, Tellides G. Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation. 2009;119:1424-1432.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 320]  [Cited by in F6Publishing: 321]  [Article Influence: 21.4]  [Reference Citation Analysis (0)]
87.  Roselaar SE, Kakkanathu PX, Daugherty A. Lymphocyte populations in atherosclerotic lesions of apoE -/- and LDL receptor -/- mice. Decreasing density with disease progression. Arterioscler Thromb Vasc Biol. 1996;16:1013-1018.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 118]  [Cited by in F6Publishing: 129]  [Article Influence: 4.6]  [Reference Citation Analysis (0)]
88.  Gewaltig J, Kummer M, Koella C, Cathomas G, Biedermann BC. Requirements for CD8 T-cell migration into the human arterial wall. Hum Pathol. 2008;39:1756-1762.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 61]  [Cited by in F6Publishing: 62]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
89.  Olofsson PS, Söderström LA, Wågsäter D, Sheikine Y, Ocaya P, Lang F, Rabu C, Chen L, Rudling M, Aukrust P. CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice. Circulation. 2008;117:1292-1301.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 170]  [Cited by in F6Publishing: 173]  [Article Influence: 10.8]  [Reference Citation Analysis (0)]
90.  Zhou X, Hansson GK. Detection of B cells and proinflammatory cytokines in atherosclerotic plaques of hypercholesterolaemic apolipoprotein E knockout mice. Scand J Immunol. 1999;50:25-30.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 93]  [Cited by in F6Publishing: 98]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
91.  Ait-Oufella H, Herbin O, Bouaziz JD, Binder CJ, Uyttenhove C, Laurans L, Taleb S, Van Vré E, Esposito B, Vilar J. B cell depletion reduces the development of atherosclerosis in mice. J Exp Med. 2010;207:1579-1587.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 302]  [Cited by in F6Publishing: 319]  [Article Influence: 22.8]  [Reference Citation Analysis (0)]
92.  Kyaw T, Tay C, Khan A, Dumouchel V, Cao A, To K, Kehry M, Dunn R, Agrotis A, Tipping P. Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis. J Immunol. 2010;185:4410-4419.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 212]  [Cited by in F6Publishing: 232]  [Article Influence: 16.6]  [Reference Citation Analysis (0)]
93.  van Leeuwen M, Damoiseaux J, Duijvestijn A, Tervaert JW. The therapeutic potential of targeting B cells and anti-oxLDL antibodies in atherosclerosis. Autoimmun Rev. 2009;9:53-57.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 44]  [Cited by in F6Publishing: 46]  [Article Influence: 3.1]  [Reference Citation Analysis (0)]
94.  Tsimikas S, Brilakis ES, Lennon RJ, Miller ER, Witztum JL, McConnell JP, Kornman KS, Berger PB. Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events. J Lipid Res. 2007;48:425-433.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 181]  [Cited by in F6Publishing: 193]  [Article Influence: 10.7]  [Reference Citation Analysis (0)]
95.  Nilsson J, Nordin Fredrikson G, Schiopu A, Shah PK, Jansson B, Carlsson R. Oxidized LDL antibodies in treatment and risk assessment of atherosclerosis and associated cardiovascular disease. Curr Pharm Des. 2007;13:1021-1030.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 34]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
96.  Nilsson J, Kovanen PT. Will autoantibodies help to determine severity and progression of atherosclerosis? Curr Opin Lipidol. 2004;15:499-503.  [PubMed]  [DOI]  [Cited in This Article: ]
97.  Salonen JT, Ylä-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssönen K, Palinski W, Witztum JL. Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet. 1992;339:883-887.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 985]  [Cited by in F6Publishing: 862]  [Article Influence: 26.9]  [Reference Citation Analysis (0)]
98.  Palinski W, Tangirala RK, Miller E, Young SG, Witztum JL. Increased autoantibody titers against epitopes of oxidized LDL in LDL receptor-deficient mice with increased atherosclerosis. Arterioscler Thromb Vasc Biol. 1995;15:1569-1576.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 142]  [Cited by in F6Publishing: 156]  [Article Influence: 5.4]  [Reference Citation Analysis (0)]
99.  Shaw PX, Hörkkö S, Chang MK, Curtiss LK, Palinski W, Silverman GJ, Witztum JL. Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J Clin Invest. 2000;105:1731-1740.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
100.  Nilsson J, Hansson GK, Shah PK. Immunomodulation of atherosclerosis: implications for vaccine development. Arterioscler Thromb Vasc Biol. 2005;25:18-28.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 79]  [Cited by in F6Publishing: 90]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
101.  Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006;6:508-519.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1558]  [Cited by in F6Publishing: 1568]  [Article Influence: 87.1]  [Reference Citation Analysis (0)]
102.  Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med. 2007;13:587-596.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 881]  [Cited by in F6Publishing: 917]  [Article Influence: 53.9]  [Reference Citation Analysis (0)]
103.  Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovasc Res. 2008;79:360-376.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 423]  [Cited by in F6Publishing: 455]  [Article Influence: 28.4]  [Reference Citation Analysis (0)]
104.  Hansson GK, Nilsson J. Vaccination against atherosclerosis? Induction of atheroprotective immunity. Semin Immunopathol. 2009;31:95-101.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 47]  [Article Influence: 3.1]  [Reference Citation Analysis (0)]
105.  van Puijvelde GH, Hauer AD, de Vos P, van den Heuvel R, van Herwijnen MJ, van der Zee R, van Eden W, van Berkel TJ, Kuiper J. Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis. Circulation. 2006;114:1968-1976.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 132]  [Cited by in F6Publishing: 138]  [Article Influence: 7.7]  [Reference Citation Analysis (0)]
106.  Wong BW, Meredith A, Lin D, McManus BM. The biological role of inflammation in atherosclerosis. Can J Cardiol. 2012;28:631-641.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 122]  [Cited by in F6Publishing: 126]  [Article Influence: 10.5]  [Reference Citation Analysis (0)]