Age-Related Features of the Viscosity of Plasma and Mitochondrial Membranes of Hepatocytes in Liver Cirrhosis.

The viscosity of plasma and mitochondrial membranes of hepatocytes was studied in young (3-month-old) and old (9-month-old) male Wistar rats. It was shown that viscosity of hepatocyte plasma and mitochondrial membranes in young rats under optimal vital functions in the area of protein-lipid membrane contacts was significantly lower than in old rats. No age-related differences in the viscosity of lipid-lipid membrane contacts and in the polarity of protein-lipid contacts and lipid layers were found. Liver cirrhosis induced by carbon tetrachloride and ethanol administration was associated with increased fluidity of the plasma and mitochondrial membranes of hepatocytes in rats of both age groups. The decrease in membrane viscosity in young rats occurred due to a decrease of the viscosity in the area of protein-lipid and lipid-lipid contacts, while in old rats in the area of protein-lipid contacts. Carbon tetrachloride and ethanol did not affect the polarity of lipid contacts and lipid layers.

Age-Related Features of the Response of the Liver and Stem Cells during Modeling of Liver Cirrhosis.

We studied the age-related characteristics of the response of stem cells and liver in male Wistar rats to administration of carbon tetrachloride (CCl4) and ethanol. It was shown that modeling of liver cirrhosis caused inflammation, fibrosis, damage to sinusoidal capillaries, necrosis, and disturbances in the functional activity of hepatocytes in young rats. These processes were accompanied by mobilization of profibrotic mesenchymal stem cells (MSC), proinflammatory hematopoietic stem cells (HSC) and lymphocytes (CD45hiCD133+) from the bone marrow into the blood and migration to the liver. On the other hand, the number of hepatocyte precursors expressing Sox9 (cells of Hering's canal), immature cholangiocytes, Ito cells, oval cells, and endothelial cells of the liver sinusoids) sharply increased in the liver. In young rats, mobilization and migration of MSC, HSC, and hepatocyte precursors against the background of liver cirrhosis were more intensive than in old animals. The higher resistance of old rats to exposure is associated with age-related changes in the niches as well as in mobilization and migration of cells.

Genetic Factors as the Basis of Sex Differences in Damage to Lung Endothelium and Regulation of Angiogenesis Cells in Modeling Pulmonary Emphysema in C57BL/6 Mice with Dyslipidemia and Hyperglycemia.

We studied the formation of injuries in lung endothelium and the response of angiogenesis cells during modeling of pulmonary emphysema in male and female C57BL/6 mice with metabolic disorders. Hemodynamic disturbances and reduction in the area of the microvasculature caused by combined pathology in male mice were more pronounced than in females. Mobilization and migration of angiogenic precursors were impaired in both male and female mice. In males, activity of recruiting endothelial progenitor cells, vascular smooth muscle cells, luminal cells of nascent vessels and pericytes into the lungs was additionally reduced. In females, accumulation of endothelial progenitor cells (CD45-CD31+CD34+), vascular smooth muscle cells, and pericytes in the lungs was observed, which indicated activation of endothelial regeneration. Sex differences in the reaction of the lung endothelium and angiogenesis cells can be explained by genetic factors of lipid and glucose metabolism.

Pericytes and Smooth Muscle Cells Circulating in the Blood as Markers of Impaired Angiogenesis during Combined Metabolic Impairments and Lung Emphysema.

The changes in endothelial progenitor cells and progenitor cells of angiogenesis, pericytes and smooth muscle cells, were studied in female C57BL/6 mice with a combination of metabolic impairments induced by injections of sodium glutamate and lung emphysema modeled by the administration of cigarette smoke extract. It was observed that sodium glutamate significantly enhances pathological changes in the lungs (inflammation and lung emphysema) induced by the administration of cigarette smoke extract. Recruiting of endothelial progenitor cells (CD45-CD31+CD34+ and CD31+CD34+CD146-) and progenitor cells of angiogenesis (CD45-CD117+CD309+) was registered in the injured lungs. Angiogenesis impairment induced by combined exposure is related to altered migration of pericytes (CD31-CD34-CD146+) and smooth muscle cells (CD31-CD34+CD146+) in emphysema-like enlarged lung tissue.

[Microviscosity of erythrocyte membranes in chronic coronary insufficiency in patients of middle and older age groups].

We examined the ratios microviscosity in the area of integral and annularly lipid membranes of erythrocytes of peripheral blood in patients of 35-50 and 60-75 years with chronic ischemic heart disease, as well as age-matched healthy controls. In healthy donors coefficients microviscosity in the area of integral and annularly lipids proved to be significantly higher in the older age group (60-75 years). In CHD, regardless of the age of the patients, erythrocyte membranes can be characterized as raising and lowering the parameters microviscosity of lipid-lipid interactions. In the protein-lipid contacts for patients aged 35-50 years an increase is typical, while for patients of 60-75 years, on the contrary, a decrease of the coefficient of microviscosity. It is concluded that the values of the microviscosity of erythrocyte membranes in patients of different age groups in the development of chronic ischemic heart disease, reflect both the implementation of the general mechanisms of adaptive changes of cell membranes, and the specifics of an individual, determined by their lipid and protein composition.

[Age-related features of microviscosity of erythrocyte membranes in experimental cardiosclerosis].

The age-related changes in the coefficient of microviscosity and polarity in the area of lipid-lipid and protein-lipid contacts of erythrocyte membranes in 4 months old (group I, n = 20) and 12 months old (group II, n = 20) rats by the method of lateral diffusion of the pyrene probe were investigated. Each age group consisted of 10 intact animals and animals after postinfarction cardiac remodeling (PICS). An increase of microviscosity and polarity of the annular and total lipids of erythrocyte membranes in 12-month animals was found. When modeling PICS in 4-month animals is pronounced increase the polarity and microviscosity of erythrocyte membranes in the annular and total lipids. The 12-month animals after PICS demonstrate a decrease of microviscosity in a lipid bilayer, and its increase in the area of annular lipids for consistently high-polarity lipids.

[Age-related features of intracellular calcium homeostasis in rat cardiomyocites in postinfarction heart remodeling].

Research results of features of an intracellular calcium homeostasis in 4 and 12-month's rat cardiomyocites at postinfarction cardiosclerosis are presented. It is shown that the myocardium of animals in the old rats group is more susceptible to extrasystolic impacts. In the pathology conditions additional extrasystolic influences also had the expressed age specificity of inotropic response. The data testifying to almost identical dynamics of postextrasystolic cycles of intact myocardium in animals of investigated age groups has been obtained. The different postextrasystolic potentiation in the remodeled myocardium in old and young rats testified to different of sarcoplasmic reticulum ability to accumulate additional calcium ions. The conclusion was made that the myocardium of animals in the old rats group has more chance for development of hemodynamic significant disturbance of cardiac rhythm as a consequence of age-related changes processes of the electromechanical coupling in cardiomyocites.

[Effect of nonselective beta-adrenoblocker carvedilol on extrasystolic and postextrasystolic contractility in the rat myocardium after experimental infarction].

Features of the extrasystolic and postextrasystolic contractility of myocardium isolated from rats aged 4 months (group I, n = 30) and 12 months (group II, n = 30) after postinfarction remodeling of the heart (PIRH) and long-term treatment with carvedilol have been studied. Each age group included in 10 intact control animals, 10 animals with postinfarction cardiosclerosis (PICS), and 10 rats with PICS treated with carvedilol (2.1 mg/kg) during 28 days, beginning with the 45th day after coronary occlusion. The isometric contractility of myocardium was monitored at an electric stimulation frequency of 0.5 Hz. The extrasystolic effect was produced by an electric pulse applied within 0.2 - 5 s interval after the basic stimulation. It is established that the inotropic response of myocardium to the extrasystolic impulse exhibits age-dependent features both the intact rats and in the rats with PICS. The differences can be related to the age-dependent involvement of the ion-transport systems of sarcolemma and sarcoplasmic reticulum into the modulation of excitation--contractility coupling during PIRH. The long-term treatment with carvedilol led to restoration of the Ca(2+)-accumulation reserve of sarcoplasmic reticulum to the age-normal level in young animalsand decreased the risk of development of hemodynamically significant heart rate disturbances in old rats.