title: Overexpression of vasostatin-1 protects hypoxia/reoxygenation injuries in cardiomyocytes independent of endothelial cells.
abstract: BACKGROUND
  Vasostatin-1 (VS-1) has been suggested in protecting hypoxia/reoxygenation (H/R) injuries in isolated hearts. However, the molecular mechanisms remained to be elucidated.
  
  
  METHODS
  Cardiomyocytes were treated with recombinant Ad-VS-1 adenoviral vector before H/R. Cell viability was studied using MTT methods and annexin V-FITC flow cytometry. Intracellular oxidative stress was measured by superoxide dismutase (SOD) and malondialdehyde (MDA), and inflammatory reactions by enzyme-linked immunosorbent assay (ELISA). Measurement of myocardial nitrous oxide synthase (NOS) was determined by serum nitric oxide (NO) concentrations using nitrite reductase and endothelial nitric oxide synthase (eNOS) by Western blotting. Inhibitors of the NOS system, including hemoglobin and KT5823, were applied to verify the results.
  
  
  RESULTS
  In comparison of the blank group, cardiac myocytes overexpressing VS-1 showed significant decrease in apoptosis, intracellular oxidative stress, and inflammatory reactions (P < 0.05). In addition, serum NO concentrations and expression of eNOS were notably enhanced (P < 0.05). These protective effects of VS-1 were suppressed in the presence of apoptosis-inducing agents.
  
  
  CONCLUSIONS
  Overexpression of VS-1 in cardiomyocytes could limit the H/R injuries at molecular levels. The protective effects were independent of endothelial cell function, suggestive of a potential therapeutic target for patients with myocardial ischemia in the future.
authors: Department of Cardiovascular Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors: Min
authors: M
authors: Yu
authors: Zheng
authors: Z
authors: Wang
authors: Yue
authors: Y
authors: Fang
authors: Ming-di
authors: MD
authors: Xiao
authors: Zhong-xiang
authors: ZX
authors: Yuan
authors: Cheng-bao
authors: CB
authors: Lu
authors: Lei
authors: L
authors: Lin
authors: Di-Cheng
authors: DC
authors: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism*; D019610:Cytoprotection; D042783:Endothelial Cells / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D053379:Chromogranin A; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D010446:Peptide Fragments; C064110:vasostatin I; D009569:Nitric Oxide; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase