EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Támogató:
EFOP
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.