title: Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction.
abstract: BACKGROUND
  Shed membrane microparticles circulate in the peripheral blood of nonischemic (NI) patients and patients with myocardial infarction (MI). We investigated whether or not these microparticles would affect endothelium-dependent responses.
  
  
  RESULTS
  Rat aortic rings with endothelium were exposed for 24 hours to circulating microparticles isolated from 7 patients with NI syndromes and 19 patients with acute MI. Endothelium-dependent relaxations to acetylcholine were not affected by high concentrations of microparticles from NI patients (P=0.80). However, significant impairment was observed in preparations exposed to microparticles from patients with MI at low and high concentrations, corresponding to 0.7-fold and 2-fold circulating plasma levels (P=0.05 and 0.001, respectively). Impairment was not affected by diclofenac (P=0.47), nor by the cell-permeable superoxide dismutase mimetic Mn(III)tetra(4-benzoic acid) porphyrin chloride (P=0.33), but it was abolished by endothelium removal or by N(omega)monomethyl-L-arginine. Relaxations to the calcium ionophore ionomycin were decreased in rings exposed to microparticles from MI patients (P=0.05 and 0.009 for low and high concentrations, respectively), but microparticles from NI patients had no effect (P=0.81). Finally, high concentrations of microparticles from MI patients affected neither endothelium-independent relaxation to sodium nitroprusside (P=0.59) nor expression of the endothelial nitric oxide synthase (P=0.43).
  
  
  CONCLUSIONS
  Circulating microparticles from patients with MI selectively impair the endothelial nitric oxide transduction pathway and, therefore, could contribute to the general vasomotor dysfunction observed after MI, even in angiographically normal arteries.
authors.affiliation: INSERM U541, IFR-Circulation, Service de Cardiologie, Hôpital Lariboisière, Paris, France. cboulang@infobiogen.fr
authors.forename: C M
authors.initials: CM
authors.lastname: Boulanger
authors.forename: A
authors.initials: A
authors.lastname: Scoazec
authors.forename: T
authors.initials: T
authors.lastname: Ebrahimian
authors.forename: P
authors.initials: P
authors.lastname: Henry
authors.forename: E
authors.initials: E
authors.lastname: Mathieu
authors.forename: A
authors.initials: A
authors.lastname: Tedgui
authors.forename: Z
authors.initials: Z
authors.lastname: Mallat
mesh_terms: D000328:Adult; D000818:Animals; D001011:Aorta; D002462:Cell Membrane / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007476:Ionophores; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004008:Diclofenac; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat