Circulating Endothelial Microparticles Are Associated with... : Journal of the American Society of Nephrology (original) (raw)

Clinical Nephrology

Circulating Endothelial Microparticles Are Associated with Vascular Dysfunction in Patients with End-Stage Renal Failure

Amabile, Nicolas*; Guérin, Alain P.†; Leroyer, Aurélie*; Mallat, Ziad*; Nguyen, Clément*; Boddaert, Jacques*; London, Gérard M.†; Tedgui, Alain*; Boulanger, Chantal M.*

*Institut National de la Santé et de la Recherche Médicale, Cardiovascular Research Center INSERM Lariboisie[Combining Grave Accent]re, Unit 689, Paris; and †Nephrology Department Centre Hospitalier Manhes, Fleury Mérogis, France

Address correspondence to: Dr. Chantal M. Boulanger, Cardiovascular Research Center, INSERM Lariboisie[Combining Grave Accent]re Hospital 41 bd de la Chapelle, 75475 Paris cedex 10, France. Phone: 33-1-5321-6686; Fax: 33-1-4281-3128; [email protected]

Accepted August 4, 2005

Received May 20, 2005

Abstract

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.