Homocysteine, Hydrogen sulfide (H₂S) and NMDA-Receptor in Heart Failure

Abstract

Mitochondrial mechanism of oxidative stress and matrix metalloproteinase (MMP) activation was unclear. Our recent data suggested that MMPs are localized to mitochondria and activated by peroxynitrite, which causes cardiovascular remodeling and failure. Recently, we have demonstrated that elevated levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy) increase oxidative stress in the mitochondria. Although HHcy causes heart failure, interestingly, it is becoming very clear that Hcy can generate hydrogen sulfide (H₂S), if the enzymes cystathionine β-synthase (CBS) and cystathionine <img src='/image/spc_char/gamma2.gif' border=0>-lyase (CGL) are present. H₂S is a strong anti-oxidant and vasorelaxing agent. Paradoxically, it is interesting that Hcy, a precursor of H₂S can be cardioprotective. The CGL is ubiquitous, while the CBS is not present in the vascular tissues. Therefore, under normal condition, only half of Hcy can be converted to H₂S. However, there is strong potential for gene therapy of CBS to vascular tissue that can mitigate the detrimental effects of Hcy by converting it to H₂S. This scenario is possible, if the activities of both the enzymes (CBS and CGL) are increased in tissues by gene therapy.