Hydrogen Sulfide Improves Vascular Calcification Through Inhibiting Endoplasmic Reticulum Stress In Rats

Objective: It was investigated that hydrogen sulfide(H2S) could ameliorate vascular calcification(VC) via prevented endoplasmic reticulum stress(ERS).Methods: The VC model of rats was induced by administration of vitamin D3(300,000 IU/kg intramuscularly) plus nicotine(25 mg/kg in 5 ml peanut oil, intragastrically)(VDN). Alizarin red staining of aorta was used to detect the calcium deposition. Aortic calcium content, aortic and plasma alkaline phosphatase(ALP) activity was detected. Hemodynamic parameters were measured by the intubation of right carotid artery. Western blot was used to observe the expression level of protein, including the marker protein of contraction phenotype of vascular smooth muscle cells(SM22 alpha and calponin-1), the marker of osteogenesis phenotype(RUNX2 and BMP2), and the marker of ERS(GRP78, CHOP and active-caspase12).Results: Compared with control group, the aorta calcium contents, the aorta and plasma ALP activity and systolic blood pressure(SBP) were significantly increased in VDN rats. The protein levels of SM22α and calponin were down-regulated in calcified aorta, while the protein levels of BMP2 and RUNX2 were up-regulated. Na SH(56μmol/kg, intraperitoneal) could ameliorate the aboved indices in VDN rats. Interestingly, the protein expression of GRP78, CHOP and active-caspase12 significantly increased in calcified aorta, and Na SH could prevent the up-regulation. Tunicamycin(TM, an inducer of ERS) could block the ameliorated effects of Na SH on VC. The effect of Na SH on calcification was as similar as that of 4-phenyl butyric acid(PBA, an inhibitor of ERS).Conclusion: These results suggested that H2 S could ameliorate the VC of rats through inhibited ERS, which might provide the new strategy and target for prevention and therapy of VC.