title: Enhanced cardiac production of matrix metalloproteinase-2 and -9 and its attenuation associated with pravastatin treatment in patients with acute myocardial infarction.
abstract: Previous experimental studies have demonstrated that MMPs (matrix metalloproteinases) contribute to LV (left ventricular) remodelling. We hypothesized that cardiac MMPs are activated in patients with AMI (acute myocardial infarction) and, if so, MMP production may be attenuated by statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) through their cardiovascular protective actions. We studied 30 patients, ten control patients with stable angina pectoris and 20 patients with AMI, in whom LV catheterization at the chronic stage was performed 22+/-12 days (value is mean+/-S.D.) after the onset of AMI. Blood samples were collected from the CS (coronary sinus) and a peripheral artery. In patients with AMI, the levels of MMP-2 and MMP-9 were significantly (P<0.05) higher in the CS than the peripheral artery (MMP-2, 853+/-199 compared with 716+/-127 ng/ml; MMP-9, 165+/-129 compared with 98+/-82 ng/ml), whereas no significant differences were observed in the patients with angina pectoris. The CS-arterial concentration gradients of MMP-2 and MMP-9 correlated positively with BNP (brain natriuretic peptide) levels (MMP-2, R=0.68, P<0.01; MMP-9, R=0.59, P<0.05) and LV end-diastolic volume index (MMP-2, R=0.70, P<0.01; MMP-9, R=0.70, P<0.01). When patients with AMI treated with 10 mg of pravastatin or without (n=10 in each group) were compared, this statin therapy significantly (P<0.05) decreased the CS-arterial concentration gradients of MMP-2 (69+/-43 compared with 213+/-185 ng/ml) and MMP-9 (14+/-27 compared with 119+/-84 ng/ml). In conclusion, the enhanced production of cardiac MMP-2 and MMP-9 is associated with LV enlargement and elevated BNP levels in patients with AMI. A pleiotropic effect of statins appears to be associated with the modulation of cardiac MMP activation, which may be potentially beneficial in the attenuation of post-infarction LV remodelling.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. syasuda@cardio.med.tohoku.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
authors.forename: Munetake
authors.initials: M
authors.lastname: Kanda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonogi
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017035:Pravastatin / Q000627:therapeutic use*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy; D020257:Ventricular Remodeling
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020097:Natriuretic Peptide, Brain; D019716:Tissue Inhibitor of Metalloproteinase-2; D002097:C-Reactive Protein; D002784:Cholesterol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017035:Pravastatin