Rosuvastatin given during reperfusion decreases infarct size and inhibits matrix metalloproteinase-2 activity in normocholesterolemic and hypercholesterolemic rabbits.
There is evidence that statin treatment before ischemia protects myocardium from ischemia/reperfusion injury. The objective is to determine whether rosuvastatin administered during reperfusion modifies infarct size and the recovery of postischemic ventricular dysfunction in normocholesterolemic and hypercholesterolemic rabbits. In addition, we also evaluated the role of matrix metalloproteinase type 2 (MMP)-2 activation. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and 120 minutes of reperfusion. In group 2, we added rosuvastatin after 30 minutes of ischemia and from the beginning of reperfusion. In group 3, an MMP inhibitor (doxycycline) was administered during the first 2 minutes of reperfusion. Finally, we repeated these groups but in hypercholesterolemic rabbits (groups 4, 5, and 6). The infarct size was 16.6% +/- 3.9% in group 1 and 25.6% +/- 2.7% in group 4. Rosuvastatin reduced infarct size to 4.5% +/- 1.1% and 6.1% +/- 1.5% in groups 2 and 5, respectively (P < 0.05). Rosuvastatin significantly decreased MMP-2 activity during reperfusion, and doxycycline induced an inhibition of MMP-2 activity and a reduction of infarct size in normocholesterolemic (4.9% +/- 0.9%) and hypercholesterolemic animals (8.3% +/- 1.6%) (P < 0.05). Rosuvastatin reduces infarct size and attenuates MMP-2 activity. These data and the correlation between MMP-2 and infarct size suggest that MMP-2 plays an important role in the mechanisms of cardioprotection afforded by rosuvastatin.
D'Annunzio
Verónica
V
Institute of Cardiovascular Pathophysiology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, Argentina.
Donato
Martín
M
Erni
Lukas
L
Miksztowicz
Verónica
V
Buchholz
Bruno
B
Carrión
Cristina Lorenzo
CL
Schreier
Laura
L
Wikinski
Regina
R
Gelpi
Ricardo J
RJ
Berg
Gabriela
G
Basso
Nidia
N
D000818:Animals; D004318:Doxycycline / Q000494:pharmacology; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D020778:Matrix Metalloproteinase 2; D004318:Doxycycline