Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3 plus nicotine in rats

Aim: To investigate the role of the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H2S) pathway in vascular calcification in vivo. Methods: A rat vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN). The amount of CSE and osteopontin (OPN) mRNA was determined by using semi-quantitative reverse-transcription polymerase chain reaction. The calcium content, Ca-45(2+) accumulation and alkaline phosphatase (ALP) activity were measured. H2S production and CSE activity were measured. Results: von Kossa staining produced strong positive black/brown staining in areas among the elastic fibers of the medial layer in the calcified aorta. The calcium content, Ca-45(2+) accumulation and ALP activity in calcified arteries increased by 6.77-, 1.42-, and 1.87-fold, respectively, compared with controls. The expression of the OPN gene was upregulated (P < 0.01). Expression of the CSE gene was downregulated. However, calcium content, Ca-45(2+) uptake and ALP activity in the VDN plus NaHS group was lower than that in the VDN group. The content of calcium and Ca-45(2+) accumulation and activity of ALP in the aorta were 34.8%, 40.75% and 63.5% lower in the low-dosage NaHS group than in the VDN group, respectively (P < 0.01), and the calcium content and deposition of Ca-45(2+) and activity of ALP was 83.9%, 37.8 % and 46.2% lower in the aorta in the high-dosage NaHS group than in the VDN group, respectively (P < 0.01). The expression of the OPN gene was downregulated. Conclusion: The production of H2S, and CSE activity were decreased and CSE gene expression was downregulated in rats with vascular calcification. H2S can ameliorate vascular calcification, suggesting that the H2S/CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.