Induction of RISK by HMG-CoA reductase inhibition affords cardioprotection after myocardial infarction.
2009, Atherosclerosis. 2009 Feb 20. [Epub ahead of print]
Vilahur G, Casaní L, Peña E, Duran X, Juan-Babot O, Badimon L.
Related authors of the center Casaní Laura, Juan Oriol, Peña Esther, Vilahur Gemma.
Vilahur G, Casaní L, Peña E, Duran X, Juan-Babot O, Badimon L.
Related authors of the center Casaní Laura, Juan Oriol, Peña Esther, Vilahur Gemma.
Cardiovascular Research Center, CSIC-ICCC, Barcelona Spain; Hospital de la Santa Creu i Sant Pau, CIBEROBN-Instituto Salud Carlos III, Barcelona, Spain.
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-1alpha 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.
PMID: 19419716 [PubMed - as supplied by publisher
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-1alpha 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.
PMID: 19419716 [PubMed - as supplied by publisher
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