Role of Oxidative Stress in Hyperhomocysteinemia-Induced Heart Diseases

Abstract

Evidence suggests that HHcy is closely related with risk of unwanted cardiovascular events. In state of excessively high levels of Hcy, metabolism of Hcy is disrupted and vascular tissue is exposed to its adverse effects. Based on epidemiological, retrospective, and prospective studies, hyperhomocysteinemia is considered as an independent risk factor for coronary heart and cerebrovascular and peripheral artery diseases. A considerable number of studies have been conducted in order to reveal the mechanisms through which Hcy contributes to endothelial injury. Endothelial dysfunction is characterized by impaired endothelium-dependent relaxation due to a decrease in available nitric oxide (NO). Hcy exerts harmful effects on vascular endothelium and smooth muscle cells, leading to impairment of arterial structure and function. The underlying mechanisms involve an increase in coagulation, synthesis of collagen, proliferation of vascular smooth muscle cells, initiation of inflammatory response, and elevated generation of pro-oxidants. Redox homeostasis is regulated by several intermediates involved in the methionine cycle, such as glutathione, hydrogen sulfide (H2S), and S-adenosyl methionine (SAM). Glutathione and H2S are responsible for regulation of cellular redox state, while SAM is a main methyl donor in organisms, and is involved in the methylation pathway of Hcy. The exact mechanism(s) of HHcy-induced endothelial dysfunction has(ve) not been fully clarified. However, it’s been proposed that endothelial dysfunction may be mediated by initiation of ROS production and reduction in capacity of antioxidant defense system. Therefore, in this chapter, we tried to consolidate current findings regarding role of oxidative stress in hyperhomocysteinemia.