During cell activation, multiple eukaryotic cells, such as endothelial cells or leukocytes, but also prokaryotes, have the ability to shed little cell blebs, so called microparticles[1,2]. Microparticles consist of the cell membrane as well as of the cytoplasm of their maternal cells and can be classified by flow cytometry into for example endothelial microparticles (EMPs), leukocyte microparticles and platelet microparticles (PMPs). When microparticles were first described by Wolf[3] over 40 years ago, it was suggested that they are only a kind of cellular debris. However, within the last couple of years microparticles have gained increasing interest in different medical fields and recent effort has been undertaken to investigate the biology of microparticles, as well as the impact of microparticles on different diseases[4-7]. It thereby has become evident that microparticles can be used as circulating surrogate markers for several pathophysiological conditions, such as inflammation, coagulation but also metastatic diseases and additionally are important circulating biological vectors[1].

The biology of microparticles is still incompletely understood, but it is evident that microparticles have far more functions than only activating inflammatory cells and the coagulation cascade. It recently has been shown that they bind to and fuse with distinct target cells, a process that is at least partly mediated by specific interactions of microparticles with surface receptors (such as Mac-1) of the target cell[8]. By fusion with their target cells, microparticles deliver cytoplasm as well as membrane anchored surface receptors to their destination cells. This process is frequently associated with changes of the target cells phenotype and function. Hence, microparticles are an own kind of biological vectors modulating the function of their target cells remote from the location where they initially had been released.

Elevated microparticle levels can often be found in pathological conditions which are associated with cell mediated inflammation and coagulation. To assess the inflammatory effect of platelet microparticles, which is the largest microparticle fraction in the blood, Jy et al[9] investigated the effect of PMPs on neutrophils. They found that microparticles released from platelets attach to neutrophils and activate those. Hence, platelet microparticles may in fact be an additional link between vascular coagulation and inflammation in cardiovascular disease.

Hypothesizing that microparticles might not only influence the phenotype but also the transcriptome of their target cells, Hunter et al[10] assessed whether microparticles from mononuclear cells contain microRNAs, which are small non-coding RNA molecules that regulate mRNA translation and thereby affect post transcriptional gene expression. In this ground breaking study, they found that microparticles indeed contain a broad spectrum of different microRNAs, which they might deliver to their target cells and presumably affect the target cells protein synthesis. Interestingly, when compared to microRNA patterns of their cells of origin, microparticles do not contain a random set of microRNAs of their paternal cells, but are loaded with a distinct, specific selection of miRNAs[11]. These findings suggest that microparticle release is a highly regulated process in which cell vesicles are “loaded” from their cells of origin with specific RNA molecules which might eventually be transferred to their target cells. However, to date the underlying molecular mechanisms of this loading process are not understood.

To what extent circulating microparticles are involved in intercellular signalling was demonstrated by a pivotal study of Janowska-Wieczorek et al[12]. They found that PMPs transfer the platelet surface receptor glycoprotein (GP)IIb/IIIa to the surfaces of different lung cancer cell lines. As the GPIIb/IIIa integrin has a high affinity to (sub)endothelial antigens, tumour cells that were pre-incubated with platelet microparticles also showed increased metastasization. Hence, PMPs might be directly involved in the progression of tumour diseases.

In summary, microparticles are small cell blebs that represent a novel way of intercellular communication, which seems to be particularly relevant for inflammatory and pro-coagulatory diseases. Due to the effects on their target cells, microparticles are able to change the phenotype, the function and presumably also the transcriptome of their target cells and might be involved in the pathogenesis of several cardiovascular diseases[1].

Arterial hypertension is a multifactor disease that is strongly promoted by endothelial dysfunction[15,16]. Recent data indicate that altered, activated endothelial cells release endothelial microparticles into circulation. EMPs can be used as cellular surrogate markers for endothelial dysfunction and are increased in several diseases with an altered endothelial function, such as atherosclerosis, aortic valve stenosis and pulmonary hypertension[17-20]. It recently was published that endothelial microparticles are even associated with several cardiovascular risk factors in the Framingham Heart Study[21].

However, besides their role as surrogate markers, microparticles are furthermore involved in the progression of impaired endothelial function as well as in angiogenesis[22,23]. For example Burger et al[24] assessed the effect of microparticles on endothelial inflammation and found that microparticles themselves induce endothelial expression of vascular cell adhesion molecule 1, platelet endothelial cell adhesion molecule and adhesion of J774A.1 cells, which is a cell line with macrophage characteristics[24]. Along the same line of evidence, Boulanger et al[25] investigated the mechanisms how microparticles induce endothelial dysfunction and found that MPs from patients with myocardial infarction, but not from healthy controls, induced endothelial dysfunction by impairing the endothelial nitric oxide transduction pathway. These data were confirmed by Martin et al[26] who discovered that T cell microparticles reduced endothelial nitric oxide- and prostacyclin mediated vasodilatation and decreased expression levels of endothelial nitric oxide synthase.

One of the few studies investigating the interconnection between microparticles and arterial hypertension was performed by Preston et al[20]. They assessed the abundance of endothelial microparticles in patients with untreated severe hypertension vs those with mild hypertension compared to normotensive individuals. It was found that microparticles released from endothelial cells and platelets were significantly increased in patients with severe arterial hypertension and that endothelial microparticles correlated strongly with the level of both systolic and diastolic blood pressures. Thus, it can be suggested that EMPs and PMPs can be used as circulating markers for endothelial injury in arterial hypertension. The findings described by Preston et al[20] are supported by studies, in which increased levels of circulating endothelial microparticles had been found in patients with pre-eclampsia, a disease that is characterized by vascular inflammation, altered endothelial function and arterial hypertension[27,28].

The Renin Angiotensin System (RAS) plays a key role in arterial hypertension and is the target for anti-hypertensive medical treatment. It has been supposed that angiotensin II, which is the final effector of the RAS, not only affects the blood pressure but furthermore induces a pro-thrombotic state. Hypothesizing that the RAS might be involved in the generation of pro-thrombotic microparticles, Cordazzo et al[29] investigated the effect of angiotensin II on the release of microparticles from mononuclear cells. They found that angiotensin II indeed induces shedding of pro-thrombotic MP from mononuclear cells. The data of Cordazzo support the suggestion that microparticles might in fact be the link between the activation of the renin angiotensin system and a pro-thrombotic state, which can be found in patients suffering from arterial hypertension.

End-organ damage, such as hypertensive nephropathy with impaired kidney function, is a common complication of patients with arterial hypertension. To assess whether endothelial microparticles might be involved in impaired renal function under arterial hypertension, Hsu et al[30] measured endothelial microparticles, endothelial progenitor cells (EPCs) and the glomerular filtration rate in patients suffering from arterial hypertension. They found that elevated EMPs to EPCs ratios are associated with a decline of the glomerular filtration rate in hypertensive patients. These data underline the impact of endothelial damage assessed by the EMP to EPC ratio on the progression of impaired kidney functions in arterial hypertensive patients.

In conclusion, particularly endothelial microparticles can be found in several conditions that are associated with arterial hypertension. EMPs are not only valuable surrogate markers reflecting the extent of endothelial cell dysfunction but additionally might promote the progression of arterial hypertension and its complications.