Metabolic and structural changes in the myocardium of rats with hypercholesterolemia after prolonged administration of simvastatin

Abstract

BACKGROUND: The use of statins in cardiovascular pathologies in some cases is associated with the risk of developing statin-induced myopathy, the mechanisms of which are not fully understood. Only a few studies of molecular changes in the myocardium in statin myopathy are presented in the literature. However, the myocardium, as a type of muscle tissue, can also be involved in the pathological process. In this regard, in our opinion, it is advisable to analyze the biochemical changes in the rat myocardium against the background of the use of simvastatin.

AIM: To analysis of the dynamics of changes in the end products of glycolysis and the isoform composition of the giant protein titin in the heart muscle in animals with experimental hypercholesterolemia on the background of long-term administration of simvastatin.

MATERIALS AND METHODS: The study was carried out on outbred male rats divided into 3 groups: control group (35 individuals) — intact animals; comparison group (35 animals) — intact animals treated with simvastatin for two months; experimental group — divided into: subgroup 1 (35 individuals) — animals with induced alimentary hypercholesterolemia, subgroup 2 (35 individuals) — animals with induced alimentary hypercholesterolemia, which were administered simvastatin for two months. During the experiment, the content of the giant sarcomere protein titin, as well as changes in the concentration of pyruvate and lactic acid in the myocardium of the animals of the studied groups were studied.

RESULTS: In animals with a physiological course of metabolic processes, the administration of simvastatin caused the accumulation of lactic acid in the myocardium. Under conditions of alimentary hypercholesterolemia under the influence of simvastatin, a decrease in the elevated level of pyruvate and lactic acid was revealed, which is obviously due to a decrease in pathobiochemical shifts in energy metabolism. The determination of the isoform composition of titin made it possible to establish that the administration of simvastatin under conditions of alimentary hypercholesterolemia contributed to the appearance of early dystrophic changes in the myocardium, which is consistent with the results of earlier studies of impaired myocardial contractile activity under the influence of statins.

CONCLUSIONS: The results obtained indicate the need for a more thorough study of statins in terms of their safe use in patients with cardiovascular pathology.

Keywords

statins / statin myopathy / simvastatin / myocardium / titin / lactic acid / pyruvate / hypercholesterolemia

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