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.

[1]  A. Bissery,et al.  Arterial and renal consequences of partial genetic deficiency in tissue kallikrein activity in humans. , 2005, The Journal of clinical investigation.

[2]  Charles E McCulloch,et al.  Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. , 2004, The New England journal of medicine.

[3]  J. Cockcroft,et al.  Nitric Oxide and the Regulation of Large Artery Stiffness: From Physiology to Pharmacology , 2004, Hypertension.

[4]  T. Iwasaka,et al.  Activated Platelet and Oxidized LDL Induce Endothelial Membrane Vesiculation: Clinical Significance of Endothelial Cell-Derived Microparticles in Patients With Type 2 Diabetes , 2004, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[5]  R. Nieuwland,et al.  Cellular microparticles: new players in the field of vascular disease? , 2004, European journal of clinical investigation.

[6]  M. Goligorsky,et al.  Endothelium-derived microparticles impair endothelial function in vitro. , 2004, American journal of physiology. Heart and circulatory physiology.

[7]  R. Andriantsitohaina,et al.  Shed Membrane Particles From T Lymphocytes Impair Endothelial Function and Regulate Endothelial Protein Expression , 2004, Circulation.

[8]  M. Safar,et al.  Arterial stiffness and kidney function. , 2004, Hypertension.

[9]  P. Baker,et al.  Isolated microparticles, but not whole plasma, from women with preeclampsia impair endothelium-dependent relaxation in isolated myometrial arteries from healthy pregnant women. , 2003, American journal of obstetrics and gynecology.

[10]  J. Freyssinet Cellular microparticles: what are they bad or good for? , 2003, Journal of thrombosis and haemostasis : JTH.

[11]  L. Horstman,et al.  High levels of circulating endothelial microparticles in patients with acute coronary syndromes. , 2003, American heart journal.

[12]  J. Blacher,et al.  Aortic pulse wave velocity index and mortality in end-stage renal disease. , 2003, Kidney international.

[13]  C. Wanner,et al.  Endothelial dysfunction and inflammation: what is the link? , 2003, Kidney international. Supplement.

[14]  Amir Lerman,et al.  Endothelial Dysfunction: A Marker of Atherosclerotic Risk , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[15]  Richard A. Preston,et al.  Effects of Severe Hypertension on Endothelial and Platelet Microparticles , 2003, Hypertension.

[16]  R. Nieuwland,et al.  Elevated Numbers of Tissue-Factor Exposing Microparticles Correlate With Components of the Metabolic Syndrome in Uncomplicated Type 2 Diabetes Mellitus , 2002, Circulation.

[17]  Y. Otaki,et al.  Impairment of Vascular Responses to Reactive Hyperemia and Nitric Oxide in Chronic Renal Failure , 2002, Nephron.

[18]  R. Nieuwland,et al.  Microparticle subpopulations are increased in preeclampsia: possible involvement in vascular dysfunction? , 2002, American journal of obstetrics and gynecology.

[19]  A. Tedgui,et al.  Circulating Microparticles From Patients With Myocardial Infarction Cause Endothelial Dysfunction , 2001, Circulation.

[20]  C. Zoccali Cardiovascular risk in uraemic patients-is it fully explained by classical risk factors? , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[21]  G. Grau,et al.  In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. , 1999, The Journal of clinical investigation.

[22]  J. Blacher,et al.  Impact of aortic stiffness on survival in end-stage renal disease. , 1999, Circulation.

[23]  M. Hijmering,et al.  Nitric oxide production is reduced in patients with chronic renal failure. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[24]  R. Foley,et al.  Clinical epidemiology of cardiovascular disease in chronic renal disease. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[25]  A. Donker,et al.  Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients. , 1998, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[26]  M. Safar,et al.  Cardiac and arterial interactions in end-stage renal disease. , 1996, Kidney international.

[27]  B. Pannier,et al.  Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies. , 1995, Hypertension.

[28]  G. London,et al.  Cardiac hypertrophy and arterial alterations in end-stage renal disease: hemodynamic factors. , 1993, Kidney international. Supplement.

[29]  R. Nieuwland,et al.  Isolated microparticles, but not whole plasma, from women with preeclampsia impair endothelium-dependent relaxation in isolated myometrial arteries from healthy pregnant women. , 2002, American journal of obstetrics and gynecology.