The effect of hypercholesterolemia on ventricular remodeling after myocardial infarction in the rat model of myocardial infarction: role of TLR4 expression and activity

Abstract

Notable discussions have been developed over the distinctive effects of LDL and oxidized LDL (OxLDL) on myocardial functions. The aim of the present study was to investigate the effects of OxLDL on myocardium in isoproterenol (ISO)-induced myocardial infarction (MI) model. Method: Male Wistar rats were allocated in to 6 groups and receive one of the 3 formulated diets (standard, cholesterol-rich and oxidized cholesterol- rich diet). After 14 weeks, to induce MI rats in 3 groups were received ISO (100 mg/kg) for 2 consecutive days subcutaneously. Lipid profiles, electrocardiogram patterns, hemodynamic parameters, oxidative stress and inflammatory pathways activation in all groups were investigated. Results: Serum levels of LDL, cholesterol and triglycerides were significantly higher in the fat rich diet fed groups compared to control group (P<0.001). The ISO-treated rats showed a marked reduction in the R-amplitude, R–R interval, LVSP, left ventricular contractility (LVdP/dtmax), relaxation (LVdP/dtmin) and severe elevation in ST-segment, LVEDP value and oxidative stress markers including myocardium CoQ10 content and MDA level compared to the respective normal rats. High serum level of OxLDL resulted in significant exacerbation in the destructive effects of ISO on mentioned values. Additionally, heart to body weight ratio as an index of myocardial edematous and serum TNF-α , IL-β levels and MYD88 protein level and TLR4 mRNA expression as an index of inflammation was also increased significantly compared to the control and ISO group. However, changes in these parameters in rats fed with cholesterol- rich diet were not so significant that were with oxidized cholesterol. Conclusion: Generally, results indicated that the effects of high serum OxLDL level on ventricular remodeling after MI were more reliable than effects of high LDL level.