■大量证据表明,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不一致。
■本研究旨在探讨内源性H2S对血管重构的有益作用。
■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(VSMC)。给予硫氢化钠(NaHS)以提供硫化氢。血管张力,H&E染色,马尾松三色染色,蛋白质印迹和CCK8用于确定血管重塑,炎症分子的表达和VSMCs的增殖。
■内源性H2S的缺乏导致血管重构,并加重主动和被动收缩,增厚主动脉壁,胶原蛋白沉积,STAT3磷酸化增加,主动脉中PPARδ和SOCS3的产生减少,被NaHS逆转了。PPG抑制PPARδ和SOCS3的表达,刺激STAT3的磷酸化,增加炎症分子的产生和VSMCs的增殖率,这些都可以通过NaHS供应来纠正。PPARδ激动剂GW501516在PPG处理的VSMC中提供类似于NaHS的保护。PPG小鼠主动脉的主动和被动收缩加剧,上调p-STAT3和炎症分子,PPARδ激动剂GW501516治疗可以纠正PPG治疗的VSMC中下调的SOCS3和表型转化。相反,PPARδ拮抗剂GSK0660对主动脉血管收缩表现出相反的作用,与GW501516相比,p-STAT3和SOCS3在VSMC中的表达。
■总之,内源性H2S通过保留PPARδ/SOCS3抗炎信号通路保护血管重构。内源性H2S缺乏应被视为VSMCs功能障碍的危险因素。
UNASSIGNED: 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.
UNASSIGNED: This study aimed to investigate the beneficial role of endogenous H2S on vascular remodeling.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.