Effect Of Hypercholesterolemia On Myocardial Necrosis And Apoptosis In Response To Ischemia Reperfusion Injury

OBJECTIVE: Myocardial ischemia-reperfusion(I/R) injury often results in necrosis and apoptosis and may lead to cardiac dysfunction or death. This study investigates impact of hypercholesterolemia in the setting of I/R injury on myocardium. METHODS: The mid-left anterior descending coronary artery in normocholesterolemic (NCn=7) and hypercholesterolemic (HCn=7) Yucatan males were occluded for 60 min, followed by reperfusion for 120 min. Hemodynamic values were recorded. Monastryl blue/TTC staining was utilized to assess the area-at-risk (AAR) and necrosis. The expression of Bcl2, apoptosis inducing factor (AIF), total & cleaved caspase3, total & cleaved PARP, bad, BNIP3, Akt and phospho-Akt measured. The TUNEL staining utilized to assess the magnitude of apoptosis. RESULTS: Hemodynamic values of MAP (p<0.01), DLVP (p<0.01), +dP/pt (p<0.01), and −dP/pt (p<0.01) were increased 1.2 fold in HC. In HC longitudinal and horizontal segmental shortening in the AAR decreased by 49% vs. 26% (p<0.01) and 68% vs. 48% (p<0.01) at the end. The AAR was similar in both groups (36% vs. 34%, p=0.61) whereas infarct size increased 45% in HC (42% vs. 61%, p=0.01). The expression of anti-apoptotic Bcl2 decreased 2.3-fold (p<0.01) whereas pro-apoptotic PARP and BNIP3 increased 2.8-fold (p<0.01) and 1.9 fold (p<0.01) respectively in HC. Ischemia decreased Akt expression 1.6-folds (p<0.01) and phospho-Akt 1.5 fold (p<0.01) in HC, whereas increased phospho-Akt 1.9 fold (p<0.01) in NC. In HC the TUNEL+ cells increased 3.8 fold (p=0.03) in the AAR. CONCLUSIONS: This study demonstrated that hypercholesterolemia have positive ionotropic effect on myocardial function, increase infarct size in AAR, mediate pro-apoptosis and attenuate survival pathway after I/R injury.