title: Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction.
abstract: BACKGROUND
  Short-term administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, has been shown to attenuate ischemia-reperfusion injury. However, the effects of long-term administration of statins on left ventricular (LV) remodeling and failure after myocardial infarction remain unknown.
  
  
  RESULTS
  Mice were subjected to coronary artery ligation and were treated for 4 weeks with vehicle or fluvastatin (10 mg/kg per day PO). Fluvastatin increased survival (61% versus 86%; P<0.05) without affecting the infarct size (52+/-2% versus 49+/-3%; P=NS). Fluvastatin not only attenuated LV dilatation but also decreased LV end-diastolic pressure and lung weight. Furthermore, it reduced cardiac myocyte hypertrophy and interstitial fibrosis of the noninfarcted LV and also improved LV ejection performance. LV matrix metalloproteinase (MMP)-2 and MMP-13 were increased in myocardial infarction, which was attenuated in fluvastatin-treated mice.
  
  
  CONCLUSIONS
  Fluvastatin increased survival in a murine model of postinfarct heart failure, which was associated with the amelioration of LV structural remodeling and contractile failure. Moreover, these effects were associated with the attenuation of increased MMP activity. Thus, long-term treatment with fluvastatin might be beneficial also in patients with heart failure and might improve their long-term survival.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Hayashidani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shiomi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suematsu
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kinugawa
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ide
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004108:Dilatation, Pathologic / Q000517:prevention & control; D004195:Disease Models, Animal; D004452:Echocardiography; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D000077340:Fluvastatin; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D015996:Survival Rate; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D007703:Peptidyl-Dipeptidase A; D020782:Matrix Metalloproteinases