Heart rate variability (HRV) depends on various reflexes, including the baroreflex or respiratory reflex. Experimental studies have suggested that the sinoatrial node density in G protein-linked receptors may be involved. Transgenic mice, with a specific eightfold atrial overexpression of human beta 1-adrenoceptor (beta 1-AR), have been generated to evaluate the role of the atrial beta 1-AR density on HRV. The heart rate was monitored using telemetry, and the signal was analyzed using a quantitative time-frequency domain analysis, the smoothed pseudo-Wigner-Ville method, and phase portrait maps. 1) Heart rate was unchanged, but the two normal components of HRV were decreased in transgenic mice. Transgenic mice have an unshortened life span and no arrhythmias. 2) Challenge of the animals by propranolol showed no modulation of the HRV in transgenic mice compared with controls. 3) In isolated atrial strips from transgenic mice, basal contractility was increased and there was no isoproterenol-induced inotropic effect. 4) The basal level of adenosine 3',5'-cyclic monophosphate production was lowered in transgenic mice, suggesting a shift in adenylate cyclase isoforms.

Obesity is a growing problem in modern society and medicine. It closely associates with metabolic disorders such as type 2 diabetes mellitus (T2DM) and hepatic and cardiovascular diseases such as nonalcoholic fatty liver disease, atherosclerosis, myocarditis, and hypertension. Obesity is often associated with latent inflammation; however, the link between inflammation, obesity, T2DM, and cardiovascular diseases is still poorly understood. Insulin resistance is the earliest feature of metabolic disorders. It mostly develops as a result of dysregulated insulin signaling in insulin-sensitive cells, as compared to inactivating mutations in insulin receptor or signaling proteins that occur relatively rare. Here, we argue that inflammatory signaling provides a link between latent inflammation, obesity, insulin resistance, and metabolic disorders. We further hypothesize that insulin-activated PI3-kinase pathway and inflammatory signaling mediated by several IκB kinases may constitute negative feedback leading to insulin resistance at least in the fat tissue. Finally, we discuss perspectives for anti-inflammatory therapies in treating the metabolic diseases.

The adult heart contains small populations of multipotent cardiac progenitor cells (CPC) that present a convenient and efficient resource for treatment of myocardial infarction. Several clinical studies of direct CPC delivery by injection have already been performed but showed low engraftment rate that limited beneficial effects of procedure. «Cell sheet» technology has been developed to facilitate longer retention of grafted cells and show new directions for cell-based therapy using this strategy. In this study we hypothesized that СPC-based cell sheet transplantation could improve regeneration after myocardial infarction. We demonstrated that c-kit+ CPC were able to form cell sheets on temperature-responsive surfaces. Cell sheet represented a well-organized structure, in which CPC survived, retained ability to proliferate, expressed progenitor cell marker Gata-4 formed connexin-43+ gap junctions, and were surrounded by significant amount of extracellular matrix proteins. Transplantation of cell sheets after myocardial infarction resulted in CPC engraftment as well as their proliferation, migration, and differentiation; cell sheets also stimulated neovascularization and cardiomyocyte proliferation in underlining myocardium and ameliorated left ventricular remodeling. Obtained data strongly supported potential use of CPC sheet transplantation for repair of damaged heart.