title: Pravastatin prevents myocardium from ischemia-induced fibrosis by protecting vascular endothelial cells exposed to oxidative stress.
abstract: OBJECTIVE
  Statins potently prevents cardiac myocytes from acute ischemia besides chronic inhibition of cholesterol synthesis. We investigated how pravastatin preserves the cardiac function after myocardial infarction (MI).
  
  
  METHODS
  Echocardiographically comparing rats with myocardial ischemia (MI group) with those treated with pravastatin (MI/statin group), we found that cardiac contractility was statistically preserved in the MI/statin whereas it was deteriorated in MI group.
  
  
  RESULTS
  Histochemical analysis suggested that ischemia-induced cardiac fibrosis was prevented by pravastatin. Because there was no significant myocyte apoptosis reflecting myocytes loss between two groups, ischemia-induced interstitial fibrosis might affect the contractility.
  
  
  CONCLUSIONS
  We hypothesized that statin may directly affect vascular endothelial cells regulating blood supply to the myocardium rather than affecting myocytes. Pravastatin perturbed H2O2-induced endothelial NOS reduction and inhibited H2O2-increased caspase-3 activation in cultured vascular endothelial cells. These data suggested that pravastatin prevent cardiac dysfunction by acting on vascular endothelial cells. Furthermore, early administration of pravastatin to the patients during acute onset of myocardial infarction may be beneficial to prevent myocardial damage caused by fibrosis associated with ischemia.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Nishi-Shinbashi 3-25-8, Minato-ku, Tokyo, 105-8461, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Abe
authors.forename: Takehiko
authors.initials: T
authors.lastname: Izumi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Urabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Taniguchi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikewaki
authors.forename: Seibu
authors.initials: S
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000166:cytology; D005355:Fibrosis / Q000517:prevention & control*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D052250:Nitric Oxide Synthase Type III; D053148:Caspase 3; D017035:Pravastatin