Abstract
The study was designed to investigate whether endogenous sulfur dioxide (SO2) plays a role in vascular calcification (VC) in rats and its possible mechanisms. In vivo medial vascular calcification was induced in rats by vitamin D3 and nicotine for four weeks. In vitro calcification of cultured A7r5 vascular smooth muscle cells (VSMCs) was induced by calcifying media containing 5 mmol/L CaCl2. Aortic smooth muscle (SM) α-actin, runt-related transcription factor 2 (Runx2), transforming growth factor-β (TGF-β) and Smad expression was measured. VC rats showed dispersed calcified nodules among the elastic fibers in calcified aorta with increased aortic calcium content and alkaline phosphatase (ALP) activity. SM α-actin was markedly decreased, but the osteochondrogenic marker Runx2 concomitantly increased and TGF-β/Smad signaling was activated, in association with the downregulated SO2/aspartate aminotransferase (AAT) pathway. However, SO2 supplementation successfully ameliorated vascular calcification, and increased SM α-actin expression, but inhibited Runx2 and TGF-β/Smad expression. In calcified A7r5 VSMCs, the endogenous SO2/AAT pathway was significantly downregulated. SO2 treatment reduced the calcium deposits, calcium content, ALP activity and Runx2 expression and downregulated the TGF-β/Smad pathway in A7r5 cells but increased SM α-actin expression. In brief, SO2 significantly ameliorated vascular calcification in association with downregulation of the TGF-β/Smad pathway.
Highlights
Vascular calcification (VC) is a common complication of aging, atherosclerosis, hypertension, diabetes and chronic kidney disease
We found that the expression of the endogenous SO2/aspartate aminotransferase (AAT) pathway was downregulated in the calcification model both in vivo and in vitro
SO2 suppressed vascular smooth muscle cells (VSMCs) calcification, exhibiting loss of granular calcium deposits in calcified VSMCs and decreased calcium content and alkaline phosphatase (ALP) activity. These results suggest that the downregulated endogenous SO2/AAT pathway is involved in the pathogenesis of vascular calcification
Summary
Vascular calcification (VC) is a common complication of aging, atherosclerosis, hypertension, diabetes and chronic kidney disease It is closely associated with cardiovascular morbidity and mortality and is an important risk factor for many cardiovascular diseases [1,2]. Recent studies have shown that microRNA regulates several key checkpoints in the cellular processes involved in the process of VSMC phenotype transformation [4,5,6,7]. These findings suggest that the mechanism for VSMC trans-differentiation during the pathogenesis of vascular calcification is a complex multifactorial and tightly regulated process, and possibly related to the regulation of genes, molecules, and signaling pathways. The underlying molecular and cellular mechanisms for vascular calcification are still not fully understood
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