Microparticles from Patients with the Acute  Coronary Syndrome Impair Vasodilatation  by Inhibiting the Akt/eNOS-Hsp90 Signaling  Pathway.
OBJECTIVE
Endothelial dysfunction is involved in the development of the acute coronary syndrome (ACS). Plasma microparticles(MPs) from other diseases have been demonstrated to initiate coagulation and endothelial dysfunction.However, whether MPs from ACS patients impair vasodilatation and endothelial function remains unclear.


METHODS
Patients(n = 62) with ACS and healthy controls (n = 30) were recruited for MP isolation. Rat thoracic aortas were incubated with MPs from ACS patients or healthy controls to determine the effects of MPs on endothelial-dependent vasodilatation,the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the interaction of eNOS with heat shock protein 90 (Hsp90), and nitric oxide (NO) and superoxide anion(O 2 – ) production. The origin of MPs was assessed by flow cytometry.


RESULTS
MP concentrations were increased in patients with ACS compared with healthy controls. They were positively correlated with the degree of coronary artery stenosis. MPs from ACS patients impair endothelial-dependent vasodilatation, decrease both Akt and eNOS phosphorylation,decrease the interaction between eNOS and Hsp90,and decrease NO production but increase O 2 – generation in rat thoracic aortas. Endothelial-derived MPs and platelet-derived MPs made up nearly 75% of MPs.


CONCLUSIONS
Our data indicate that MPs from ACS patients negatively affect endothelial-dependent vasodilatation via Akt/eNOS-Hsp90 pathways.
Wen-Qi
WQ
Han
Feng-Jun
FJ
Chang
Qun-Rang
QR
Wang
Jun-Qiang
JQ
Pan
D054058:Acute Coronary Syndrome / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
D018841:HSP90 Heat-Shock Proteins; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt