Renoprotection by hydrogen sulfide in hyperhomocysteinemia

Abstract

Homocysteine (Hcy) is a sulfur-containing amino acid, which forms as an intermediate during methionine metabolism. High levels of plasma Hcy, also known as hyperhomocysteinemia (HHcy), are always associated with kidney insufficiency [4,5,26,31]. Results from recent studies have indicated that HHcy downregulates hydrogen sulfide (H2S) level [22] and reduces endothelial nitric oxide synthase (eNOS) [18]. In addition, through imbalance of matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP), Hcy accumulates extracellular matrix (ECM) protein in the peri-glomerular space [21,23,24]. These contribute to renovascular remodeling including renal fibrosis and dysfunction. Although Hcy is known for independent vascular risk factor, the mechanism of renal fibrosis in HHcy is largely unknown. In the tissue, Hcy however metabolizes by three endogenous enzymes: cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) to produce H 2 S, a gaseous molecule of tremendous biological importance. This editorial highlights some of the recent updates and future directions of renoprotection by H 2 S in HHcy. Significance Several mechanisms are proposed of which, a) sustained and abnormal elevation of glomerular arterial wall stress, b) initiation of complex and progressive glomerular remodeling, and c) renal microvascular impairment and vasoconstriction [20] are well documented, and may contribute to pathophysiological renal disorders during kidney insufficiency. The mechanism of glomerulosclerosis and increased wall