Imbalance of Homocysteine and H2S: Significance, Mechanisms, and Therapeutic Promise in Vascular Injury

Abstract

While the role of hyperhomocysteinemia in cardiovascular pathogenesis continuously draws attention, deficiency of hydrogen sulfide (H2S) has been growingly implicated in cardiovascular diseases. Generation of H2S is closely associated with the metabolism of homocysteine via key enzymes such as cystathionineβ-synthase (CBS) and cystathionineγ-lyase (CSE). The level of homocysteine and H2S is regulated by each other. Metabolic switch in the activity of CBS and CSE may occur with a resultant operating preference change of these enzymes in homocysteine and H2S metabolism. This paper presented an overview regarding (1) linkage between the metabolism of homocysteine and H2S, (2) mutual regulation of homocysteine and H2S, (3) imbalance of homocysteine and H2S in cardiovascular disorders, (4) mechanisms underlying the protective effect of H2S against homocysteine-induced vascular injury, and (5) the current status of homocysteine-lowering and H2S-based therapies for cardiovascular disease. The metabolic imbalance of homocysteine and H2S renders H2S/homocysteine ratio a potentially reliable biomarker for cardiovascular disease and development of drugs or interventions targeting the interplay between homocysteine and H2S to maintain the endogenous balance of these two molecules may hold an even bigger promise for management of vascular disorders than targeting homocysteine or H2S alone.