Low-density lipoprotein receptor gene transfer in hypercholesterolemic mice improves cardiac function after myocardial infarction

Abstract

Left ventricular (LV) function post-myocardial infarction (MI) is adversely influenced by hypercholesterolemia independent of the severity of coronary atherosclerosis. The objective of this study was to evaluate whether lipid lowering by adenoviral low-density lipoprotein (LDL) receptor (AdLDLr) gene transfer in C57BL/6 LDL receptor (LDLr)-deficient mice beneficially affects ventricular remodeling and cardiac function post-MI independent of effects on the coronary circulation. AdLDLr transfer reduced plasma cholesterol by 77% (PPPex vivo EPC function. LV contractility and relaxation were better preserved in AdLDLr MI mice compared with control MI mice. In conclusion, lipid lowering in hypercholesterolemic mice exerts direct cardioprotective effects resulting in enhanced survival, reduced infarct size, decreased ventricular remodeling and better cardiac function.