Hydrogen Sulfide Prevents Elastin Loss and Attenuates Calcification Induced by High Glucose in Smooth Muscle Cells through Suppression of Stat3/Cathepsin S Signaling Pathway

摘要: Vascular calcification can be enhanced by hyperglycemia. Elastin loss in tunica media promotes the osteogenic transformation of smooth muscle cells (SMCs) and involves arterial medial (AMC) that is associated with a high incidence cardiovascular risk patients type 2 diabetes. Here, we tested whether hydrogen sulfide (H2S), an endogenous gaseous mediator, prevent elastin attenuate induced glucose SMCs. Calcification was (4500 mg/L) human aortic SMCs (HASMCs) under condition calcifying medium containing 10 mM β-glycerophosphate (β-GP). The experiments showed NaHS (an H2S donor, 100 μM) mitigated HASMCs treated decreasing calcium phosphorus levels, deposition ALP activity inhibited increasing SMα-actin SM22α, two phenotypic markers cells, core binding factor α-1 (Cbfα-1), key bone formation, protein expressions HASMCs. Moreover, administration activation Stat3, cathepsin S (CAS) its expression, but increased level protein. Pharmacological inhibition or gene silencing Stat3 not only reversed loss, also attenuated CAS expression. Inhibition alleviated, while overexpression exacerbated, loss. Interestingly, wild (WT)-Stat3, mutant C259S, elevated expression reduced level. S-sulfhydration WT, C259S Stat3. These data suggest may directly regulate Cys259 residue then impair signaling function. Our indicate vascular upregulating through Stat3/CAS signaling.