Endogenous hydrogen sulfide improves vascular remodeling through PPARδ/SOCS3 signaling.
Endogenous hydrogen sulfide improves vascular remodeling through PPARδ/SOCS3 signaling.
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内源性硫化氢通过 PPAR delta/SOCS3 信号传导改善血管重塑
DOI：
10.1016/j.jare.2020.06.005
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发表时间：
2021-01
影响因子：
10.7
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Tian D;Teng X;Jin S;Chen Y;Xue H;Xiao L;Wu Y
CSE耗竭导致的H2S缺乏有助于血管重塑和血管平滑肌细胞的转化。在CSE/H2S缺乏相关的VSMCs转化过程中，PPARδ/SOCS 3信号通路减少。在CSE耗竭的条件下，减少的PPARδ负责减少的SOCS 3表达。CSE/H2S通过PPARδ保护SOCS 3的产生并抑制炎性分子的产生。越来越多的证据表明，硫化氢（H2S）的缺乏促进了心血管疾病的进展。然而，H2S对血管重塑的确切影响并不一致。本研究旨在探讨内源性H2S对血管重塑的有益作用。CSE抑制剂DL-炔丙基甘氨酸（PPG）用于治疗小鼠和血管平滑肌细胞（VSMCs）。给予硫氢化钠（NaHS）以提供硫化氢。采用血管张力、H&E染色、Masson三色染色、western blot和CCK 8检测血管重塑、炎性分子表达和VSMCs增殖。内源性H2S缺乏导致血管重构，主动和被动收缩加重，主动脉壁增厚，胶原沉积，STAT 3磷酸化增加，PPARδ和SOCS 3产生减少，NaHS可逆转上述变化。PPG抑制VSMCs的PPARδ和SOCS 3表达，刺激STAT 3磷酸化，增加VSMCs的炎症分子产生和增殖速率，NaHS可纠正PPG的抑制作用。在PPG处理的VSMC中，PPARδ激动剂GW 501516提供类似于NaHS的保护。PPG处理的VSMCs中，PPG小鼠血管平滑肌的主动和被动收缩加重，p-STAT 3和炎症分子上调，SOCS 3下调和表型转化可通过PPARδ激动剂GW 501516处理来纠正。而GSK 0660对血管平滑肌细胞p-STAT 3和SOCS 3表达的影响与GW 501516相反。总之，内源性H2S可能通过保护PPARδ/SOCS 3抗炎信号通路而抑制血管重构。内源性H2S缺乏是VSMCs功能障碍的危险因素
H2S deficiency derived from CSE depletion contributes to the vascular remodeling and transformation of vascular smooth muscle cells. PPARδ/SOCS3 signaling pathway is decreased in CSE/H2S deficiency-associated transformation of VSMCs. Reduced PPARδ is responsible for decreased SOCS3 expression under condition of CSE depletion. CSE/H2S preserves SOCS3 production through PPARδ and inhibits inflammatory molecules production. Mounting evidences demonstrated the deficiency of hydrogen sulfide (H2S) facilitated the progression of cardiovascular diseases. However, the exact effects of H2S on vascular remodeling are not consistent. This study aimed to investigate the beneficial role of endogenous H2S on vascular remodeling. CSE inhibitor, DL-propargylglycine (PPG) was used to treat mice and vascular smooth muscle cells (VSMCs). Sodium hydrosulfide (NaHS) was given to provide hydrogen sulfide. Vascular tension, H&E staining, masson trichrome staining, western blot and CCK8 were used to determine the vascular remodeling, expressions of inflammatory molecules and proliferation of VSMCs. The deficiency of endogenous H2S generated vascular remodeling with aggravated active and passive contraction, thicken aortic walls, collagen deposition, increased phosphorylation of STAT3, decreased production of PPARδ and SOCS3 in aortas, which were reversed by NaHS. PPG inhibited expression of PPARδ and SOCS3, stimulated the phosphorylation of STAT3, increased inflammatory molecules production and proliferation rate of VSMCs which could all be corrected by NaHS supply. PPARδ agonist GW501516 offered protections similar to NaHS in PPG treated VSMCs. Aggravated active and passive contraction in PPG mice aortas, upregulated p-STAT3 and inflammatory molecules, downregulated SOCS3 and phenotype transformation in PPG treated VSMCs could be corrected by PPARδ agonist GW501516 treatment. On the contrary, PPARδ antagonist GSK0660 exhibited opposite effects on vascular contraction in aortas, expressions of p-STAT3 and SOCS3 in VSMCs compared with GW501516. In a word, endogenous H2S protected against vascular remodeling through preserving PPARδ/SOCS3 anti-inflammatory signaling pathway. Deficiency of endogenous H2S should be considered as a risk factor for VSMCs dysfunction
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影响因子：
7.7
作者：
Serrano-Marco L;Rodríguez-Calvo R;El Kochairi I;Palomer X;Michalik L;Wahli W;Vázquez-Carrera M
通讯作者：
Vázquez-Carrera M
影响因子：
10.8
作者：
Durham AL;Speer MY;Scatena M;Giachelli CM;Shanahan CM
通讯作者：
Shanahan CM
影响因子：
11.1
作者：
Degueurce G;D'Errico I;Pich C;Ibberson M;Schütz F;Montagner A;Sgandurra M;Mury L;Jafari P;Boda A;Meunier J;Rezzonico R;Brembilla NC;Hohl D;Kolios A;Hofbauer G;Xenarios I;Michalik L
通讯作者：
Michalik L
影响因子：
5
作者：
El-Sayed SS;Zakaria MN;Abdel-Ghany RH;Abdel-Rahman AA
通讯作者：
Abdel-Rahman AA
影响因子：
5.6
作者：
Cao, Yan-jun;Zhang, Yan-min;He, Lang-chong
通讯作者：
He, Lang-chong