Hydrogen sulfide inhibits the calcification and osteoblastic differentiation of vascular smooth muscle cells

Abstract

Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is involved in the pathogenesis of vascular calcification. Hydrogen sulfide (H2S) is a gas endogenously produced by cystathionine γ-lyase in VSMC. Here we determined whether H2S plays a role in phosphate-induced osteoblastic transformation and mineralization of VSMC. Hydrogen sulfide was found to inhibit calcium deposition in the extracellular matrix and to suppress the induction of the genes involved in osteoblastic transformation of VSMC: alkaline phosphatase, osteocalcin, and Cbfa1. Moreover, phosphate uptake and phosphate-triggered upregulation of the sodium-dependent phosphate cotransporter (Pit-1) were also prevented by H2S. Reduction of endogenous production of H2S by inhibition of cystathionine γ-lyase activity resulted in increased osteoblastic transformation and mineralization. Low plasma levels of H2S, associated with decreased cystathionine γ-lyase enzyme activity, were found in patients with chronic kidney disease receiving hemodialysis. Thus, H2S is a potent inhibitor of phosphate-induced calcification and osteoblastic differentiation of VSMC. This mechanism might contribute to accelerated vascular calcification in chronic kidney disease.

Hydrogen Sulfide Inhibits Abnormal Proliferation of Lymphocytes via AKT/GSK3� Signal Pathway in Systemic Lupus Erythematosus Patients

“…What's more, HS-NSAIDs did not induce leukocyte adherence whereas NSAIDs did [23]. These studies provide the clues for H 2 S treatment to SLE, such as gastrointestinal protection, anti-inflammatory vasodilatation and so on [24]. The results of this study provided evidence for therapeutic prospect of H 2 S to SLE, suppressing the abnormal proliferation of lupus lymphocytes.…”

Calcification of vascular smooth muscle cells is induced by secondary calciprotein particles and enhanced by tumor necrosis factor-α

“…In vitro calcification of VSMC has been widely studied using calcification medium, i.e. cell culture medium supplemented with phosphate, calcium and FBS [25,40,47,48]. Using this approach, however, calcification induction was initially variable in our hands.…”

H2S and Blood Vessels: An Overview

“…Supplement of NaHS significantly reduced aortic calcium mineral deposits, OPN mRNA expression, and ALP activity, pointing to a regulatory role of CSE/H 2 S pathway in the pathogenesis of vascular calcification. By using cultured SMCs, Zavaczki et al explored the roles of H 2 S in phosphateinduced osteoblastic transformation and mineralization (Zavaczki et al 2011). H 2 S inhibited calcium deposition in the extracellular matrix and suppressed the induction of the genes involved in osteoblastic transformation of SMCs, including alkaline phosphatase, osteocalcin, and Cbfa1.…”