Endothelium-derived microparticles impair endothelial function in vitro.
Endothelial cell dysfunction (ECD) is emerging as the common denominator for diverse and highly prevalent cardiovascular diseases. Recently, an increased number of procoagulant circulating endothelial microparticles (EMPs) has been identified in patients with acute myocardial ischemia, preeclampsia, and diabetes, which suggests that these particles represent a surrogate marker of ECD. Our previous studies showed procoagulant potential of endothelial microparticles and mobilization of microparticles by PAI-1. The aim of this study was to test the effects of isolated EMPs on the vascular endothelium. EMPs impaired ACh-induced vasorelaxation and nitric oxide production by aortic rings obtained from Sprague-Dawley rats in a concentration-dependent manner. This effect was accompanied by increased superoxide production by aortic rings and cultured endothelial cells that were coincubated with EMPs and was inhibited by a SOD mimetic and blunted by an endothelial nitric oxide synthase inhibitor. Superoxide was also produced by isolated EMP. In addition, p22(phox) subunit of NADPH-oxidase was detected in EMP. Our data strongly suggest that circulating EMPs directly affect the endothelium and thus not only act as a marker for ECD but also aggravate preexisting ECD.
Brodsky
Sergey V
SV
Department of Medicine, New York Medical College, Valhalla, New York 10595, USA. sergey_brodsky@nymc.edu
Zhang
Fan
F
Nasjletti
Alberto
A
Goligorsky
Michael S
MS
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001777:Blood Coagulation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D026901:Membrane Transport Proteins / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019255:NADPH Oxidases; D010316:Particle Size; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation
D016166:Free Radical Scavengers; D026901:Membrane Transport Proteins; D008665:Metalloporphyrins; D010750:Phosphoproteins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013481:Superoxides; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase