Diet-Induced Hypercholesterolemia Leads to Cardiac Dysfunction and Alterations in the Myocardial Proteome

Abstract

Elevated blood cholesterol is a major risk factor for coronary heart disease. Moreover, direct effects on the myocardium also contribute to the adverse effects of hypercholesterolemia. Here, we investigated the effect of hypercholesterolemia on the cardiac proteome. Male Wistar rats were fed with a laboratory rodent chow supplemented with 2% cholesterol for 8 weeks to induce hypercholesterolemia. The protein expression data obtained from the proteomic characterization of left ventricular samples from normo- and hypercholesterolemic animals were subjected to gene ontology (GO) and protein interaction analyses. Elevated circulating cholesterol levels were accompanied by diastolic dysfunction in cholesterol-fed rats. The proteomic characterization of left ventricular samples revealed altered expression of 45 proteins due to hypercholesterolemia. Based on the Gene Ontology analysis, hypercholesterolemia was associated with disturbed expression of cytoskeletal and contractile proteins. Beta-actin was downregulated in the hypercholesterolemic myocardium, and established a prominent hub of the protein interaction network. Analysis of the unfiltered dataset revealed concordant downregulated expression patterns in proteins associated with the arrangement of the contractile system (e.g., cardiac-specific troponins and myosin complex), and in subunits of the mitochondrial respiratory chain. We conclude that the observed changes in the cardiac proteome may contribute to the development of diastolic dysfunction in hypercholesterolemia.

Effects of Thymoquinone Alone or in Combination with Losartan on the Cardiotoxicity Caused by Oxidative Stress and Inflammation in Hypercholesterolemia

“…As a direct result of high LDL-C levels, atherosclerosis has become a substantial risk factor for ischemic heart disease, one of the world's most prevalent causes of death [3]. It has been shown previously that hypercholesterolemia has a direct influence on heart function, which ultimately results in the following impairments: contractile dysfunction [4,5]; exacerbation of ischemia/reperfusion [6]; and decreased response to cardioprotective treatments such as ischemic pre-and post-conditioning [7]. The pathobiology of hypercholesterolemia has been investigated, but the underlying molecular pathways that cause heart problems remain unclear.…”