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- Li, Zhenzhen, et al.
(författare)
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Endogenous Sulfur Dioxide Inhibits Vascular Calcification in Association with the TGF-beta/Smad Signaling Pathway
- 2016
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 17:3
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Tidskriftsartikel (refereegranskat)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) alpha-actin, runt-related transcription factor 2 (Runx2), transforming growth factor-beta (TGF-beta) 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 alpha-actin was markedly decreased, but the osteochondrogenic marker Runx2 concomitantly increased and TGF-beta/Smad signaling was activated, in association with the downregulated SO2/aspartate aminotransferase (AAT) pathway. However, SO2 supplementation successfully ameliorated vascular calcification, and increased SM alpha-actin expression, but inhibited Runx2 and TGF-beta/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-beta/Smad pathway in A7r5 cells but increased SM alpha-actin expression. In brief, SO2 significantly ameliorated vascular calcification in association with downregulation of the TGF-beta/Smad pathway.
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| 2. |
- Yao, Qiuyu, et al.
(författare)
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The vasodilatory effect of sulfur dioxide via SGC/cGMP/PKG pathway in association with sulfhydryl-dependent dimerization
- 2016
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6119 .- 1522-1490. ; 310:11, s. R1073-R1080
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Tidskriftsartikel (refereegranskat)abstract
- The present study was designed to explore the role of soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/PKG pathway in sulfur dioxide (SO2)-induced vasodilation. We showed that SO2 induced a concentration-dependent relaxation of phenylephrine (PE)precontracted rat aortic rings in association with an increase in cGMP concentration, whereas L-aspartic acid beta-hydroxamate (HDX), an inhibitor of SO2 synthase, contracted rings in a dose-dependent manner. Pretreatment of aortic rings with the sGC inhibitor ODQ (30 mu M) attenuated the vasodilatory effects of SO2, suggesting the involvement of cGMP pathway in SO2-induced vasodilation. Mechanistically, SO2 upregulated the protein levels of sGC and PKG dimers, while HDX inhibited it, indicating SO2 could promote cGMP synthesis through sGC activation. Furthermore, the dimerization of sGC and PKG and vasodilation induced by SO2 in precontracted rings were significantly prevented by thiol reductants dithiothreitol (DTT). In addition, SO2 reduced the activity of phosphodiesterase type 5 (PDE5), a cGMP-specific hydrolytic enzyme, implying that SO2 elevated cGMP concentration by inhibiting its hydrolysis. Hence, SO2 exerted its vasodilatory effects at least partly by promoting disulfide-dependent dimerization of sGC and PKG, resulting in an activated sGC/cGMP/PKG pathway in blood vessels. These findings revealed a new mode of action and mechanisms by which SO2 regulated the vascular tone.
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