Hydrogen sulfide prevents arterial medial calcification in rats with diabetic nephropathy

Abstract

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 μmol/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-γ-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 SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-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-β1 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-β1 level and increasing local elastin level.

Hydrogen Sulfide Suppresses Skin Fibroblast Proliferation via Oxidative Stress Alleviation and Necroptosis Inhibition

“…Additionally, previous studies found that H 2 S inhibited the activation of fibrosis-related cells and cytokine expression, then alleviated renal fibrosis, and improved renal function in the rats with renal sclerosis caused by renal tubular epithelial mesenchymal transition (EMT) [ 18 ]. Exogenous H 2 S significantly decreased the level of TGF- β 1 in vivo , increased the expression of aortic elastin, and prevented diabetic nephropathy arteriosclerosis in rats [ 19 ]. H 2 S improved myocardial fibrosis via suppressing the TGF- β 1 /Smad signaling pathway [ 20 ].…”

Endothelium-Mimicking Bilayer Vascular Grafts with Dual-Releasing of NO/H2S for Anti-Inflammation and Anticalcification

“…H 2 S, as an important mediator in numerous physiological processes, has the effects of antioxidation, anti-inflammation, antiapoptosis, cytoprotection, and pro-angiogenesis. Exogenous H 2 S supplementation can alleviate the occurrence of vascular calcification by maintaining the contractile phenotype of HUASMCs and inhibiting the osteogenic phenotype differentiation of HUASMCs. , Moreover, H 2 S can inhibit the absorption of phosphate by inhibiting the expression of Pit-1 on the membrane of HUASMCs, and play an antiarterial calcification effect via scavenging oxides to combat oxidative stress. It is inferred that PLCL/KS//PLCL/SH-Cu mats released H 2 S under the trigger of GSH to reduce intracellular and extracellular calcium deposition and inhibit the expression of genes involved in the HUASMCs osteogenic transformation to alleviate arterial calcification.…”

The many roles of cathepsins in restenosis

“…As a result, this process significantly impacts the advancement of hypertension [ 88 , 89 ]. Numerous experimental studies conducted in vivo and in vitro have provided evidence that H 2 S can upregulate elastin levels by inhibiting Stat3/CatS signaling, and can prevent elastin loss and degradation, thereby stabilizing HASMCs as contractile VSMCs (Marker: SM α-actin and SM22α) and decreasing vascular calcification [ 90 , 91 ].…”