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Endogenous hydrogen sulfide improves vascular remodeling through PPARδ/SOCS3 signaling
Author(s) -
Tian Danyang,
Wu Yuming,
Teng Xu,
Jin sheng,
Chen Yuhong
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08917
Subject(s) - sodium hydrosulfide , vascular smooth muscle , socs3 , downregulation and upregulation , agonist , endogeny , chemistry , signal transduction , endocrinology , medicine , phosphorylation , pharmacology , receptor , stat3 , biochemistry , hydrogen sulfide , organic chemistry , smooth muscle , gene , sulfur
Mounting evidences demonstrated the deficiency of hydrogen sulfide (H 2 S) implicated the progression of cardiovascular diseases. This study aimed to investigate the beneficial role of endogenous H 2 S on vascular remodeling in CSE inhibitor, DL‐propargylglycine (PPG), treated mice. The deficiency of endogenous H 2 S exhibited aggravated active and passive contraction, coupled with thicken aortic walls, vascular remodeling with collagen deposition, increased phosphorylation of STAT3 and decreased PPARδ, SOCS3, which were reversed by sodium hydrosulfide chronic treatment for 4 weeks. Aggravated active and passive contraction, upregulated p‐STAT3, downregulated SOCS3 in PPG mice aortas could be corrected by PPARδ agonist GW501516. On the contrary, PPARδ antagonist GSK0660 exhibited opposite effects on vascular contraction, expressions of p‐STAT3, SOCS3 in aortas. PPG inhibited expression of PPARδ and SOCS3, stimulated the phosphorylation of STAT3, inflammatory molecules production in vascular smooth muscle cells (VSMCs). PPARδ agonist normalized the phenotype transformation from contractile to synthetic in both PPG mice aortas and PPG treated VSMCs. NaHS offered similar functions with PPARδ agonist. In a word, endogenous H 2 S benefits against vascular remodeling through preserving PPARδ/SOCS3 inflammatory signaling pathway. Deficiency of endogenous H 2 S should be considered as a risk factor for VSMCs dysfunction. Support or Funding Information This study was supported by the National Natural Science Foundation of China (Grant 31671185, 31871154, 91849120), the Natural Science Foundation of Hebei Province of China (H2017206269), the Hebei Province for Innovation Talents Support Plan (Grant LJRC017), and the Research Foundation for Higher Education of Hebei Province (GCC2014032, ZD2019027).The loss of endogenous H2S aggravated LPS‐induced myocardial dysfunction.