Abstract 628: Circulating Microparticles From Patients With Valvular Heart Disease and Cardiac Surgery Inhibit Endothelium Dependent Vasodilation.

Abstract

Objective: Circulating microparticles (MPs) from some diseases play important roles on inflammation, coagulation and vascular injury. The vascular function is quite important for maintaining the circulation after cardiac surgery. However, the impact of MPs generated from valvular heart disease (VHD) and cardiac surgery on vascular function remains unknown. The present study is to investigate the impact of such MPs on vasodilation. Methods: MPs were isolated from age-match healthy subjects and patients with VHD before and at 12 h, 72 h after cardiac surgery. Effects of MPs on vasodilation of mice aorta, the phosphorylation and expression of Akt, protein kinase C βII (PKC-βII), p70S6K, endothelial nitric oxide synthase (eNOS) and caveolin-1, the association of eNOS with heat shock protein 90 (HSP90), generation of nitric oxide (NO) and superoxide anion (O2•–) of human umbilical vein endothelial cells (HUVECs) were determined. Results: Compared with MPs from healthy subjects, MPs from VHD patients before cardiac surgery can impair endothelium-dependent vasodilation, inhibit phosphorylation of Akt and eNOS, enhance expression of caveolin-1, and activation of PKC-βII, p70S6K, and reduced association of HSP90 with eNOS, decrease NO production and increase O2•– generation. Those effects were even stronger when treated with MPs from post- cardiac surgery. Conclusion: Our data demonstrated that circulating MPs generated before and after cardiac surgery in VHD patients contributed to endothelial dysfunction by inhibiting and uncoupling of eNOS activity. Circulating MPs may be a potential therapeutic target for maintenance of vascular function post-cardiac surgery.