Endothelial dysfunction and arterial stiffness are major determinants of cardiovascular risk in patients with end-stage renal failure (ESRF). Microparticles are membrane fragments shed from damaged or activated cells. Because microparticles can affect endothelial cells, this study investigated the relationship between circulating microparticles and arterial dysfunction in patients with ESRF and identified the cellular origin of microparticles associated with these alterations. Flow cytometry analysis of platelet-free plasma from 44 patients with ESRF indicated that circulating levels of Annexin V؉ microparticles were increased compared with 32 healthy subjects, as were levels of microparticles derived from endothelial cells (three-fold), platelets (16.5-fold), and erythrocytes (1.6-fold). However, when arterial function was evaluated noninvasively in patients with ESRF, only endothelial microparticle levels correlated highly with loss of flow-mediated dilation (r ‫؍‬ ؊0.543; P ‫؍‬ 0.004), increased aortic pulse wave velocity (r ‫؍‬ 0.642, P < 0.0001), and increased common carotid artery augmentation index (r ‫؍‬ 0.463, P ‫؍‬ 0.0017), whereas platelet-derived, erythrocyte-derived, and Annexin V؉ microparticle levels did not. In vitro, microparticles from patients with ESRF impaired endothelium-dependent relaxations and cyclic guanosine monophosphate generation, whereas microparticles from healthy subjects did not. Moreover, in vitro endothelial dysfunction correlated with endothelial-derived (r ‫؍‬ 0.891; P ‫؍‬ 0.003) but not platelet-derived microparticle concentrations. In fact, endothelial microparticles alone decreased endothelial nitric oxide release by 59 ؎ 7% (P ‫؍‬ 0.025). This study suggests that circulating microparticles of endothelial origin are tightly associated with endothelial dysfunction and arterial dysfunction in ESRF.J (3,4), a systemic disorder and a key variable in the pathogenesis of atherosclerosis and its complications (5). Moreover, arterial wall stiffening, which is partly influenced by nitric oxide (NO) and the endothelium (6,7), occurs frequently during ESRF and has been reported as an independent predictor of cardiovascular events (7-9) Circulating microparticles (MP) are shed membrane vesicles resulting from apoptosis or activation of several cell types in response to various stimuli (10,11). We previously demonstrated that circulating MP that are isolated from patients with acute coronary syndromes directly induce endothelial dysfunction in vitro and hypothesized that this effect could be of clinical relevance (12). In this study, we sought to extend those earlier observations by investigating the possible relationships between circulating MP levels and in vivo arterial properties in patients with ESRF. In addition, we undertook to determine the cellular origin of the circulating MP associated with these vascular alterations. Materials and MethodsWe included 44 patients with ESRF from the Fleury-Mérogis hemodialysis center. Patients were eligible for inclusion when (1) they had ha...

Membrane vesicles released in the extracellular space are composed of a lipid bilayer enclosing soluble cytosolic material and nuclear components. Extracellular vesicles include apoptotic bodies, exosomes, and microvesicles (also known previously as microparticles). Originating from different subcellular compartments, the role of extracellular vesicles as regulators of transfer of biological information, acting locally and remotely, is now acknowledged. Circulating vesicles released from platelets, erythrocytes, leukocytes, and endothelial cells contain potential valuable biological information for biomarker discovery in primary and secondary prevention of coronary artery disease. Extracellular vesicles also accumulate in human atherosclerotic plaques, where they affect major biological pathways, including inflammation, proliferation, thrombosis, calcification, and vasoactive responses. Extracellular vesicles also recapitulate the beneficial effect of stem cells to treat cardiac consequences of acute myocardial infarction, and now emerge as an attractive alternative to cell therapy, opening new avenues to vectorize biological information to target tissues. Although interest in microvesicles in the cardiovascular field emerged about 2 decades ago, that for extracellular vesicles, in particular exosomes, started to unfold a decade ago, opening new research and therapeutic avenues. This Review summarizes current knowledge on the role of extracellular vesicles in coronary artery disease, and their emerging potential as biomarkers and therapeutic agents.

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