Immunohistochemical Analysis of MMP-2 Expression in the Myocardium During the Postinfarction Period.

Immunohistochemical analysis revealed 2.5-fold increased of expression MMP-2 in myocardium samples during the early period (up to 3 days) of postinfarction reparative regeneration. During this period, MMP-2 was detected mainly in monocytes/macrophages circulating in the blood and migrating to the necrotic zone, while expression in the intermuscular and perivascular connective tissue was lower. At later terms, with development of large focal and diffuse cardiosclerosis, MMP-2 expression significantly decreased (to the initial level) and was detected mainly in the foci of intermuscular and perivascular fibrosis, its area in the sections increased by 1.8 times. Evaluation of MMP-2 expression in the blood vessels showed that the immunohistochemical reaction was the most pronounced in the walls of new sinusoidal vessels and the minimum in the intramural arteries of medium diameter. These results attest to an important role of MMP in connective tissue remodeling (proteolytic degradation) during the early period of postinfarction reparative regeneration. The decrease in MMP-2 expression observed at later terms correlated with myocardial fibrosis progression.

Morphological Evaluation of Oxidative Phosphorylation System in Myocardial Infarction under Conditions of Modified Vascular Endothelial Growth Factor Concentration.

The relationship between vascular endothelium growth factor (VEGF) and cardiomyocyte oxidative phosphorylation level in experimental myocardial infarction, caused by diathermocoagulation of the periconical ventricular artery, was studied by immunofluorescent microscopy. Staining showed uneven distribution of cytochrome c in the mitochondria in the focus of myocardial infarction 2 h after the operation. After 24 h uneven staining of cardiomyocytes was found in the peri-infarction zone and no staining in the zone of myocardial infarction. This indicated a significant decrease in the level of redox enzymes. This picture persisted till day 14. Intraventricular injection of VEGF to animals led to a significant increase of the immunohistochemical reaction intensity, which reached the peak by day 7. The distribution of immunohistochemical reaction products under conditions of VEGF blocking was about the same as in spontaneous postinfarction reparative restitution. Our data indicated that increase of VEGF concentration in the myocardium maintained and stimulated oxidative phosphorylation in cardiomyocytes during the postinfarction period.

Mitral and Aortic Valvulitis in Primary Chronic Septic Endocarditis.

Results of long-term prospective follow-up of patients with early stages of mitral and aortic valvulitis and primary chronic septic endocarditic are presented. Clinical diagnostics of the diseases is described and the key role is assigned to pathognomic (absolute) clinical symptoms. The tendency to progressive fibrosis of endocardial structures with subsequent gradual development of valve dysfunction and stenosis (especially for the mitral valve) is revealed. It is shown that early treatment increases the effective valve area and promotes reversion of mitral stenosis. The possibility of early diagnostics of primary chronic septic endocarditis in combination with adequate etiopathogenetic therapy provide the basis for prevention of acquired valvular disease.

Content of circulating extracellular DNA, plasma activities of matrix metalloproteinases, and ultrastructure of the myocardium in hypothyroid rats with hypercholesterolemia.

Free circulating extracellular DNA, plasma activities of matrix metalloproteinases in hypothyroid rats, and ultrastructural changes in the myocardium were studied under conditions of experimental hypercholesterolemia. For suppression of thyroid function, the animals received antithyroid drug mercazolyl under conditions of cholesterol diet. Hypercholesterolemia in hypothyroid rats (thyroxine concentration 2-fold below the normal) was paralleled by a pronounced increase of the concentration of free circulating extracellular DNA and total matrix metalloproteinases 2 and 7 activity. These changes were associated with lytic and destructive changes in cardiomyocytes and blood capillary endotheliocytes. Changes in the cardiomyocyte and endotheliocyte ultrastructure were more pronounced in hypothyroid rats.

Proliferative activity of cadriomyocytes in chronic hypercholesterolemia.

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.

Expression of mRNA of apolipoprotein E, apolipoprotein A-IV, and matricellular proteins in the myocardium and intensity of fibroplastic processes during experimental hypercholesterolemia.

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.

Structural changes in the myocardium and serum lipid spectrum in experimental hypercholesterolemia and hypothyroidism.

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.

Lipid spectrum in patients with atherosclerosis of various localizations.

Variants of dyslipidemias were studied in 78 patients with atherosclerosis of various localizations. We also studied HDL content and atherogenic index, which served as a predictor of polyvascular disease. Depending on localization atherosclerosis had specific features. Type II of dyslipidemia was typical for multifocal and coronary atherosclerosis, type IV was typical for brachiocephalic arteries.

Expression of heparanase-1 in prostate gland tumors.

Expression of heparanase-1 in prostate tumors was evaluated by RT-PCR, immunoblotting, and immunohistochemistry. Malignant transformation was shown to be associated with considerable increase in the expression of heparanase-1 at both mRNA and protein levels, which correlated with the degree of metastasizing and can be used as the marker for diagnostics of the metastatic process.