Endogenous hydrogen sulfide improves vascular remodeling through PPARδ/SOCS3 signaling

Abstract

Mounting evidences demonstrated the deficiency of hydrogen sulfide (H2S) implicated the progression of cardiovascular diseases. This study aimed to investigate the beneficial role of endogenous H2S on vascular remodeling in CSE inhibitor, DL‐propargylglycine (PPG), treated mice. The deficiency of endogenous H2S 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 H2S benefits against vascular remodeling through preserving PPARδ/SOCS3 inflammatory signaling pathway. Deficiency of endogenous H2S should be considered as a risk factor for VSMCs dysfunction.Support or Funding InformationThis 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.Figure 1