We studied the peculiarities of lipid spectrum of the blood and structural reorganization of the myocardium in experimental hypercholesterolemia with and without hypothyroidism. It was found that alimentary hypercholesterolemia accompanied by elevated total cholesterol, LDL, HDL, and triglyceride concentrations led to a decrease in body weight, heart weight, number of cardiomyocytes in the heart and induced pronounced lytic changes in cardiomyocytes, circulation disorders (sludge syndrome, echinocytosis of erythrocytes, lymphostasis), diffuse fibrosis of the stroma, and appearance of foam cells among diffuse mononuclear infiltrate cells. The combination of hypercholesterolemia with hypothyroid status caused more pronounced changes in the lipid spectrum and atherogenic index and more pronounced lytic and necrobiotic changes in cardiomyocytes. These findings suggest that elevated cholesterol concentrations in the blood, especially against the background of suppressed thyroid function, can directly induce considerable damage to cardiomyocytes, intramural vessels, and erythrocytes without the development of myocardial ischemia and in the absence of atherosclerotic plaques.
We studied proliferative activity of cardiomyocytes (using proliferation marker Ki-67) and compared it with their total number in the heart under conditions of experimental chronic hypercholesterolemia and its combination with hypothyroidism. It was found that Ki-67-positive cells are primarily located in the subepicardial layer near the heart base in both intact and experimental animals. Replicative cardiomyocyte pool in intact rats constituted 1.67 ± 0.33‰ of the total cardiomyocyte population; after 68-day atherogenic diet with exogenous cholesterol alone, the replicative cardiomyocyte pool decreased by 16 % (to 1.40 ± 0.24‰). Treatment with mercazolil against the background of exogenous cholesterol increased this parameter by 40 % (to 2.33 ± 0.88‰). Changes in replicative activity of cardiomyocytes correlated with their total number in the heart and organ weight. We conclude that replicative cardiomyocyte pool primarily includes non-terminally differentiated cardiomyocytes (small mononuclear cardiomyocytes) and their proliferation maintains the total number of cardiomyocytes in the heart under conditions of cytopathic influences and provides the basis for physiological and reparative regeneration of the myocardium.
The expression of mRNA of matricellular proteins (osteopontin, and lumican), apolipoproteins E and A-IV, and microsomal triglyceride transfer protein, and the intensity of fibroplastic processes were studied in the myocardium of rats during experimental chronic hypercholesterolemia. We have found that the development of chronic hypercholesterolemia was followed by an increase in volume density of interstitial connective tissue in the myocardium reflecting the activation of fibroplastic processes. A slight positive correlation was observed between the connective tissue density in the myocardium and expression of osteopontin mRNA (r=0.408) and lumican mRNA (r=0.470). Myocardium remodeling during hypercholesterolemia is realized against the background of increased expression of apolipoproteins E and A-IV mRNA and microsomal triglyceride transfer protein mRNA involved in transport and metabolism of lipoproteins in several tissues and probably play a pivotal role in the regulation of lipoprotein transport and metabolism in the myocardium. We concluded that the increase in the expression of apolipoproteins (E and A-IV) and microsomal triglyceride transfer protein play adaptive and compensatory role and is related to the increase in lipoprotein utilization by macrophages.
Significant associations between clinical history factors, lipid metabolism parameters, and type of atherosclerotic process (area of vascular lesions and severity of clinical manifestations) were detected. The predominance of generalized atherosclerosis in chronic coronary heart disease group was associated with patients' age, more incident excessive body weight and type 2 diabetes mellitus, and more severe course of arterial hypertension. Increased lipid spectrum atherogenicity was significantly more often observed in generalized atherosclerosis in the myocardial infarction group. Angiography and postmortem examination of coronary arteries detected two trends of atherogenic remodeling of the coronary vessels: more pronounced stenosis of the main vessels in autopsy specimens from myocardial infarction patients with mainly coronary atherosclerosis and more extensive coronary bed involvement in chronic coronary heart disease patients with generalized atherosclerosis.
The type and intensity of remodeling (structural reorganization) of the myocardium in Wistar rats were studied under conditions of experimental chronic dyslipidemia and verapamil treatment. Long (64 days) atherogenic diet caused dyslipidemia and led to reduction of the heart percent weight. The cytopathic effect of dyslipidemia manifested in more intense lytic injuries of cardiomyocytes, development of diffuse and small focal cardiosclerosis under conditions of manifest circulatory disorders. Remodeling of the myocardium during various periods of the experiment manifested in a higher connective tissue/cardiomyocyte volume ratio (by 74% after 30 days and by 58-62% after 64 days of experiment). Verapamil injection promoted attenuation of lytic changes in cardiomyocytes and in fibroplastic reactions of the stroma, but failed to prevent them completely.
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