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

Erzsébet Zavaczki, Viktória Jeney, Anupam Agarwal, Abolfazl Zarjou, Melinda Oros, Mónika Katkó, Zsuzsa Varga, György Balla, József Balla

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is involved in the pathogenesis of vascular calcification. Hydrogen sulfide (H 2 S) is a gas endogenously produced by cystathionine γ-lyase in VSMC. Here we determined whether H 2 S 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 H 2 S. Reduction of endogenous production of H 2 S by inhibition of cystathionine γ-lyase activity resulted in increased osteoblastic transformation and mineralization. Low plasma levels of H 2 S, associated with decreased cystathionine γ-lyase enzyme activity, were found in patients with chronic kidney disease receiving hemodialysis. Thus, H 2 S 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.

Original languageEnglish
Pages (from-to)731-739
Number of pages9
JournalKidney International
Volume80
Issue number7
DOIs
Publication statusPublished - Oct 1 2011

Keywords

  • cystathionine γ-lyase
  • hydrogen sulfide
  • vascular calcification
  • vascular smooth muscle cell

ASJC Scopus subject areas

  • Nephrology

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