title: Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function.
abstract: Mitral valve endothelial cells are important for maintaining lifelong mitral valve integrity and function. Plasma endothelial microparticles (EMPs) increased in various pathological conditions related to activation of endothelial cells. However, whether EMPs will increase in mitral valve disease and their relationship remains unclear. Here, 81 patients with mitral valve disease and 45 healthy subjects were analyzed for the generation of EMPs by flow cytometry. Human mitral valve endothelial cells (HMVECs) were treated with EMPs. The phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the association of eNOS and heat shock protein 90 (HSP90), and the generation of nitric oxide (NO) and superoxide anion (O(2)(∙-)) were measured. EMPs were increased significantly in patients with mitral valve disease compared with those in healthy subjects. EMPs were negatively correlated with mitral valve area in patients with isolated mitral stenosis. EMPs were significantly higher in the group with severe mitral regurgitation than those in the group with mild and moderate mitral regurgitation. Furthermore, EMPs were decreased dramatically in both Akt and eNOS phosphorylation and the association of HSP90 with eNOS in HMVECs. EMPs decreased NO production but increased O(2)(∙-) generation in HMVECs. Our data demonstrated that EMPs were significantly increased in patients with mitral valve disease. The increase of EMPs can in turn impair HMVEC function by inhibiting the Akt/eNOS-HSP90 signaling pathway. These findings suggest that EMPs may be a therapeutic target for mitral valve disease.
authors: Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Hong-Bo
authors: HB
authors: Ci
authors: Zhi-Jun
authors: ZJ
authors: Ou
authors: Feng-Jun
authors: FJ
authors: Chang
authors: Dong-Hong
authors: DH
authors: Liu
authors: Guo-Wei
authors: GW
authors: He
authors: Zhe
authors: Z
authors: Xu
authors: Hai-Yun
authors: HY
authors: Yuan
authors: Zhi-Ping
authors: ZP
authors: Wang
authors: Xi
authors: X
authors: Zhang
authors: Jing-Song
authors: JS
authors: Ou
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000166:cytology / Q000378:metabolism; D008944:Mitral Valve Insufficiency / Q000378:metabolism*; D008946:Mitral Valve Stenosis / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D013481:Superoxides; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt