THE ROLE OF HOMOCYSTEIN IN THE DEVELOPMENT OF CARDIOVASCULAR DISEASE
Art ZYLBEARI, Nadir AJRULI, Koço ÇAKALAROVSKI, Gazmend ZYLBEARI, Elita MASHA, Milka ZDRAVKOVSKA
Abstract
Cardiovascular diseases (CVD) are the leading cause of excess death worldwide, but to this day it is not clear how their multifactorial pathology develops. In recent years, a large number of studies have proven that the incidence of cardiovascular morbidity and mortality from CVD varies from both genetic predisposition and metabolic disorders of the methionine cycle of homocysteine (Hcy) metabolism, which leads to hyperhomocysteinemia (HHCy) and the occurrence of premature and accelerated cardiac atherosclerosis (Ath) and premature death. The impact of HHcy on the occurrence of CVD remains unclear, but it is assumed to be related to the role of H2S by increasing H2S production, which reduces the expression of adenosine A2A receptors on the surface of cardiovascular cells, activates Nuclear Factor-kappa B (NF-κB),conversion to Hcy-thiolactone and induction of autoimmune response and thrombo-genesis.Increase in proinflammatory cytokines to cause inflammation, premature atherosclerosis, myoca-rdial infarction, cerebrovascular disease, peripheral arterial disease and coronary ischemia. HHCy acts on endothelial cell permeability by inhibiting endothelial nitric oxide synthase,which produces nitric oxide (NO) leading to coronary ischemia.HHCy is a condition in which the plasma HCy concentration is elevated ≥15 μmol/L (refer.value 5-15 μmol/L), which occurs as a result of an imbalance between its biosynthesis and catabolism. Supplementation with vitamins B6,B12 and folic acid has been shown to have very positive effects on reducing homocysteine as well as on reducing vascular premature Ath changes in the coronary, cerebral and peripheral blood vessels. Previous research proposed a positive role of H2S in the cardiovascular system, and we discuss some recent data suggesting that HHcy worsens CVD by increasing the production of H2S, which decreases the expression of adenosine A2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively[1].
Pages: 94 - 99