title: Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation.
abstract: OBJECTIVE
  Vascular function is very important for maintaining circulation after cardiac surgery. Circulating microparticles (MPs) generated in various diseases play important roles in causing inflammation, coagulation, and vascular injury. However, the impact of MPs generated from patients who have valvular heart disease (VHD), before and after cardiac surgery, on vascular function remains unknown. This study is designed to investigate the impact of such MPs on vasodilation.
  
  
  METHODS
  Microparticles were isolated from age-matched healthy subjects and patients who had VHD, before cardiac surgery, and at 12 hours and 72 hours afterward. The number of MPs was measured and compared. Effects evaluated were of the impact of MPs on: vasodilation of mice aorta; the phosphorylation and expression of Akt, endothelial nitric oxide synthase (eNOS), protein kinase C-βII (PKC-βII), and p70 ribosomal protein S6 kinase (p70S6K); expression of caveolin-1; the association of eNOS with heat shock protein 90 (HSP90); and generation of nitric oxide and superoxide anion of human umbilical vein endothelial cells.
  
  
  RESULTS
  Compared with the healthy subjects, VHD patients had significantly higher levels of circulating MPs and those MPs before cardiac surgery can: impair endothelium-dependent vasodilation; inhibit phosphorylation of Akt and eNOS; increase activation of PKC-βII and p70S6K; enhance expression of caveolin-1; reduce the association of HSP90 with eNOS; decrease nitric oxide production, and increase superoxide anion generation. These deleterious effects were even stronger in postoperative MPs.
  
  
  CONCLUSIONS
  Our data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively.
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Province Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Province Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Hu
authors.affiliation: Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Province Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Ze-Bang
authors.initials: ZB
authors.lastname: Lin
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Province Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Chang
authors.affiliation: Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Province Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Division of Hypertension and Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Ou
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Wang
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Province Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address: oujs@mail.sysu.edu.cn.
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: Ou
mesh_terms: D000328:Adult; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000503:physiopathology; D006348:Cardiac Surgical Procedures; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006349:Heart Valve Diseases / Q000097:blood* / Q000503:physiopathology / Q000601:surgery*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: Microparticles; cardiac surgery; endothelial nitric oxide synthase; valvular heart disease; vasodilation