Yana Anfinogenova

Platelet hemostasis in patients with metabolic syndrome and type 2 diabetes mellitus: cGMP- and NO-dependent mechanisms in the insulin-mediated platelet aggregation.

Patients with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) have high risk of microcirculation complications and microangiopathies. An increase in thrombogenic risk is associated with platelet hyperaggregation, hypercoagulation, and hyperfibrinolysis. Factors leading to platelet activation in MetS and T2DM comprise insulin resistance, hyperglycemia, non-enzymatic glycosylation, oxidative stress, and inflammation. This review discusses the role of nitric oxide (NO) in the regulation of platelet adhesion and aggregation processes. NO is synthesized both in endotheliocytes, smooth muscle cells, macrophages, and platelets. Modification of platelet NO-synthase (NOS) activity in MetS patients can play a central role in the manifestation of platelet hyperactivation. Metabolic changes, accompanying T2DM, can lead to an abnormal NOS expression and activity in platelets. Hyperhomocysteinemia, often accompanying T2DM, is a risk factor for cardiovascular accidents. Homocysteine can reduce NO production by platelets. This review provides data on the insulin effects in platelets. Decrease in a number and sensitivity of the insulin receptors on platelets in T2DM can cause platelet hyperactivation. Various intracellular mechanisms of anti-aggregating insulin effects are discussed. Anti-aggregating effects of insulin are mediated by a NO-induced elevation of cGMP and upregulation of cAMP- and cGMP-dependent pathways. The review presents data suggesting an ability of platelets to synthesize humoral factors stimulating thrombogenesis and inflammation. Proinflammatory cytokines are considered as markers of T2DM and cardiovascular complications and are involved in the development of dyslipidemia and insulin resistance. The article provides an evaluation of NO-mediated signaling pathway in the effects of cytokines on platelet aggregation. The effects of the proinflammatory cytokines on functional activity of platelets are demonstrated.

Exercise and NO production: relevance and implications in the cardiopulmonary system

This article reviews the existing knowledge about the effects of physical exercise on nitric oxide (NO) production in the cardiopulmonary system. The authors review the sources of NO in the cardiopulmonary system; involvement of three forms of NO synthases (eNOS, nNOS, and iNOS) in exercise physiology; exercise-induced modulation of NO and/or NOS in physiological and pathophysiological conditions in human subjects and animal models in the absence and presence of pharmacological modulators; and significance of exercise-induced NO production in health and disease. The authors suggest that physical activity significantly improves functioning of the cardiovascular system through an increase in NO bioavailability, potentiation of antioxidant defense, and decrease in the expression of reactive oxygen species-forming enzymes. Regular physical exercises are considered a useful approach to treat cardiovascular diseases. Future studies should focus on detailed identification of (i) the exercise-mediated mechanisms of NO exchange; (ii) optimal exercise approaches to improve cardiovascular function in health and disease; and (iii) physical effort thresholds.

Physical exercise associated with NO production: signaling pathways and significance in health and disease

Here we review available data on nitric oxide (NO)-mediated signaling in skeletal muscle during physical exercise. Nitric oxide modulates skeletal myocyte function, hormone regulation, and local microcirculation. Nitric oxide underlies the therapeutic effects of physical activity whereas the pharmacological modulators of NO-mediated signaling are the promising therapeutic agents in different diseases. Nitric oxide production increases in skeletal muscle in response to physical activity. This molecule can alter energy supply in skeletal muscle through hormonal modulation. Mitochondria in skeletal muscle tissue are highly abundant and play a pivotal role in metabolism. Considering NO a plausible regulator of mitochondrial biogenesis that directly affects cellular respiration, we discuss the mechanisms of NO-induced mitochondrial biogenesis in the skeletal muscle cells. We also review available data on myokines, the molecules that are expressed and released by the muscle fibers and exert autocrine, paracrine and/or endocrine effects. The article suggests the presence of putative interplay between NO-mediated signaling and myokines in skeletal muscle. Data demonstrate an important role of NO in various diseases and suggest that physical training may improve health of patients with diabetes, chronic heart failure, and even degenerative muscle diseases. We conclude that NO-associated signaling represents a promising target for the treatment of various diseases and for the achievement of better athletic performance.

Nonpharmacological Correction of Hypersympatheticotonia in Patients with Chronic Coronary Insufficiency and Severe Left Ventricular Dysfunction

Control of sympathetic hyperactivity is pivotal for treatment of heart failure (HF) in patients with coronary artery disease (CAD). Our earlier studies demonstrated that the auricular pulsed electrical stimulation of the vagus nerve (VNS) beneficially affected condition of CAD patients with HF. The aim of our study was to evaluate changes in heart rate (HR) and the levels of heat shock proteins in peripheral blood lymphocytes in patients with CAD in the course of VNS.