Induction of RISK by HMG-CoA reductase inhibition affords cardioprotection after myocardial infarction
Por:
Vilahur, G, Casani, L, Pena, E, Duran, X, Juan-Babot, O, Badimon, L
Publicada:
1 sep 2009
Resumen:
Objectives: Coronary occlusion and revascularization leads to myocardial damage and heart function deterioration. Statins can regress atherosclerosis and modulate platelet function, but their effect on post-acute myocardial infarction (AMI) injury remains to be fully determined. We sought to examine whether rosuvastatin (R) exerts any effect on the RISK/apoptosis pathway when administered early after coronary reperfusion.
Methods: Pigs were fed 10 days a hypercholesterolemic diet before AMI induction and thereafter for 7 days randomly distributed to receive R or placebo (C) with the same diet. At sacrifice, hearts were sliced and alternatively collected for MI size and molecular analysis (gene and protein expression) in the peri-infarcted and remote myocardium. The RISK components (PKC, Erk2, and Akt/PKB) and downstream targets (HIF-1 alpha and VEGF), and cell survival/apoptosis markers (Bcl-2, Bax, and Caspase-3) were analyzed. Annexin-V, Mito-Tracker staining, and inflammatory infiltration were also evaluated.
Results: R enhanced PKC, Erk2, Akt/PKB and its downstream effectors, and attenuated inflammation and cardiomyocyte apoptosis in the peri-infarcted zone (p < 0.05). No changes were detected in the remote myocardium. Infarct size was smaller in R than in C pigs (7% absolute reduction: 36% relative reduction: p < 0.05) and was associated with an absolute 12% recovery of LVEF (24% relative restoration: p < 0.05 vs. post-AMI).
Conclusions: HMG-CoA inhibition early after reperfusion activates RISK kinases, reduces the extent of damaged myocardium, and improves heart function. (C) 2009 Published by Elsevier Ireland Ltd.
Filiaciones:
Vilahur, G:
CSIC ICCC, Cardiovasc Res Ctr, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, CIBEROBN Inst Salud Carlos III, Barcelona, Spain
Casani, L:
CSIC ICCC, Cardiovasc Res Ctr, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, CIBEROBN Inst Salud Carlos III, Barcelona, Spain
Pena, E:
CSIC ICCC, Cardiovasc Res Ctr, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, CIBEROBN Inst Salud Carlos III, Barcelona, Spain
Duran, X:
CSIC ICCC, Cardiovasc Res Ctr, Barcelona 08025, Spain
Juan-Babot, O:
CSIC ICCC, Cardiovasc Res Ctr, Barcelona 08025, Spain
Badimon, L:
CSIC ICCC, Cardiovasc Res Ctr, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, CIBEROBN Inst Salud Carlos III, Barcelona, Spain
UAB, Barcelona, Spain
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