Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure.
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.
Amabile
Nicolas
N
Institut National de la Santé et de la Recherche Médicale, Cardiovascular Research Center INSERM Lariboisière, Unit 689, Paris, France.
Guérin
Alain P
AP
Leroyer
Aurélie
A
Mallat
Ziad
Z
Nguyen
Clément
C
Boddaert
Jacques
J
London
Gérard M
GM
Tedgui
Alain
A
Boulanger
Chantal M
CM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D002462:Cell Membrane / Q000473:pathology; D021961:Cell Membrane Structures / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006439:Hemodynamics; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014652:Vascular Diseases / Q000097:blood / Q000473:pathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D006454:Hemoglobins; D002097:C-Reactive Protein