The effect of unmodified chitosan nanoparticles with a size of ~100 nm and a weakly positive charge on blood coagulation, metabolic activity of cultured cardiomyocytes, general toxicity, biodistribution, and reactive changes in rat organs in response to their single intravenous administration at doses of 1, 2, and 4 mg/kg was studied. Chitosan nanoparticles (CNPs) have a small cytotoxic effect and have a weak antiplatelet and anticoagulant effect. Intravenous administration of CNPs does not cause significant hemodynamic changes, and 30 min after the CNPs administration, they mainly accumulate in the liver and lungs, without causing hemolysis and leukocytosis. The toxicity of chitosan nanoparticles was manifested in a dose-dependent short-term delay in weight gain with subsequent recovery, while in the 2-week observation period no signs of pain and distress were observed in rats. Granulomas found in the lungs and liver indicate slow biodegradation of chitosan nanoparticles. In general, the obtained results indicate a good tolerance of intravenous administration of an unmodified chitosan suspension in the studied dose range.

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Endothelial dysfunction is considered as a universal non-specific link in the pathogenesis of many diseases, primarily the cardiovascular system. This review is devoted to the discussion of the main functions of the endothelium and mechanisms for their implementation. One of the most striking features of endothelial cells is their morphological heterogeneity, which allows us to identify several typical forms of endothelial dysfunction (vasomotor, hemostatic, adhesion and angiogenous). Also, the review presents the most promising predictors of cardiovascular diseases and their complications among endothelial damage markers.

These changes in the deformations may be the first signs of deterioration of the left ventricular function and the existence of primary cardiomyopathy in young adults with mitral valve prolapse, which may be caused by increased transforming growth factor-β signalling.

Objective - to identify the most accurate way of drugs endothelial protective properties evaluation. Material and methods. Blood endothelin-1 (E) and acetylcholine-induced endothelial dependent vasodilation (EDV) were measured for 9 months in type 2 diabetic patients receiving either metformin (MET) (group 1) or MET and liraglutide (LIR) (group 2). Results. E was normal in group 1 at baseline and decreased only with glycaemia decline, in group 2 it was primarily increased and declined independently on glycaemia dynamics. In both groups E normalized in 6 months. EDV was impaired primarily in groups 1 and 2 and normalized only in group 2 in 9 months. Conclusions. LIR improves endothelial function, independently on glycaemia. Dopplerography in more accurate in drugs endothelial protective effects evaluation than circulating markers.

Objective. To evaluate liraglutide (LIR) endothelial protective action. Material and methods. Type 2 diabetic patients with HbA1C 7.5-9.0 % had metformin (MET) dose titrated for 3 months. Patients with HbA1C less than 7.5 % comprised group 1 (MET), more than 7.5 % - group 2 (MET+LIR). Blood concentrations of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), endothelin-1 (E) were evaluated at baseline, in 3, 6 and 9 months. Results. PAI-1 was increased in both groups and gradually decreased. T-PA was normal. E was primarily increased only in group 2. E was normal in group 1 in general, but enlarged with glycaemia increase. E decreased in group 2 with glycaemia improvement and worsening. Conclusions. Glycaemia control improvement decreases endothelial dysfunction. LIR improves vasomotor endothelial function, independently on its influence on glycaemia.

Cardioprotective effects of necrostatin-1 (necroptosis inhibitor) and 3-methyladenine (autophagy inhibitor) were studied on the model of long-term cold preservation of rat heart. Addition of necrostatin-1 (490 nmol/liter) or 3-methyladenine (4.5 mmol/liter) to custodiol preserving solution reduced myocardial infarction size and improved left-ventricular function during reperfusion after 8-h preservation at 4°C. Inhibition of necroptosis and autophagy contributed to the cardioprotective effect under conditions of cold preservation of the donor heart.

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