Hydrogen sulfide prevents arterial medial calcification in rats with diabetic nephropathy

Background Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (H2S) can prevent AMC in rats with diabetic nephropathy (DN). Methods DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague-Dawley rats for 8 weeks. Results Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a H2S donor, 50 mu mol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous H2S generating enzyme activity and protein expression of cystathionine-gamma-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SM alpha-actin and SM22 alpha, and downregulating core binding factor alpha-1 (Cbf alpha-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-beta 1 protein level, and improved aortic elastin expression. Conclusions H2S may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-beta 1 level and increasing local elastin level.

Automated summary

H2S treatment can alleviate arterial medial calcification in rats with diabetic nephropathy by reducing calcium and phosphorus content, ALP activity, and calcium deposition, as well as restoring the activity and expression of the endogenous H2S generating enzyme CSE in the arterial wall.