A NEW LOOK AT THE PROTECTIVE ROLE OF MELATONIN IN CASE OF POLYMORBID CARDIOVASCULAR PATHOLOGY
Abstract
Over the past years, close attention of the world scientific community has been directed to the main hormone of the pineal gland — melatonin. In the course of many studies, the protective properties of this hormone were found in various pathological conditions. Thus, in a chronic inflammatory process, melatonin stimulates the production of anti-inflammatory and suppresses the activity of pro-inflammatory cytokines and neuronal NO-synthases and cyclooxygenase-2, participates in the removal of reactive oxygen species from the cell, and also optimizes mitochondrial function through mitofusin-2. Melatonin performs its antihypertensive function by regulating the renin-angiotensin system, suppressing endothelin expression, enhancing the production of nitrosyl radical and endothelial nitric oxide synthase, and also by interacting with the central nervous system by modulating melatonin activity due to GABAergic signaling in neurons from the suprachiasmatic nucleus to various parts of the central nervous system, including the ventrolateral part of the medulla oblongata. In addition, it modulates the SIRT1/mitofusin 2 pathway by reducing the production of reactive oxygen species, deactivates LDL-induced pyroptosis in endothelial cells via the MEG3/miR-223/NLRP3 axis, and inhibits serum cholesterol absorption and biosynthesis, thereby achieving a lipid-lowering effect. Another significant function of melatonin is participation in the regulation of glycemia and control of insulinemia. It reduces insulin secretion through the melatonin 1 receptor by inhibiting the adenylate cyclase — cyclic adenosine monophosphate pathway, and through the melatonin 2 receptor it inhibits the guanylate cyclase — cyclic guanosine monophosphate pathway. On the other hand, melatonin can also stimulate insulin secretion by releasing inositol triphosphate through interaction with the melatonin 2 receptor. It should be noted that the antidepressant effect of melatonin is achieved by modulating neuroplastic reactions in the hippocampus and stimulating neurogenesis, axogenesis, and dendritogenesis. Thus, melatonin is an important protective factor in polymorbid cardiovascular pathology due to its positive effect on lipid metabolism, obesity and insulin resistance, correction of arterial hypertension level of glucose, as well as antidepressant action.
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