Hydrogen Sulfide Therapy in Diabetes-Accelerated Atherosclerosis: A Whiff of Success.

Abstract

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in diabetes (1). Atherosclerosis occurs earlier and with greater severity in the population with diabetes, leading to a much higher risk of myocardial infarction, stroke, and limb ischemia and amputation. Although numerous factors contribute to the etiology of atherosclerosis, oxidative stress and inflammation play a fundamental role and both processes are exacerbated in diabetes. Given the rapidly growing worldwide incidence of diabetes, there is a critical need for new therapies that target atherogenesis and its clinical manifestations in patients with diabetes. The gasotransmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) have emerged as crucial regulators of vascular disease in diabetes (2). Although NO and CO have been extensively studied, less is known regarding the role of H2S in diabetes. H2S is a colorless, water-soluble gas with the characteristic smell of rotten eggs. It is generated by the metabolism of cysteine by the enzymes cystathionine β-synthase and cystathionine γ-lyase or by the concerted action of cysteine amino transferase and 3-mercaptopyruvate sulfurtransferase (Fig. 1). H2S is also produced nonenzymatically from glucose, glutathione, thiosulfate, and sulfur-containing proteins and by the bacterial reduction of sulfur in the intestinal tract (3,4). Although long considered a toxic gas, studies in the past decade have revealed important physiological roles for H2S. H2S promotes blood flow by dilating blood vessels and inhibiting platelet aggregation (3,5). It also exerts potent antioxidant, antiapoptotic, anti-inflammatory, and angiogenic responses. H2S …