H 2 S attenuates oxidative stress via Nrf2/NF-κB signaling to regulate restenosis after percutaneous transluminal angioplasty

• Published in: Experimental biology and medicine (Maywood, N.J.) N.J.), 2021-01, Vol.246 (2), p.226-239
• Main Authors: Ling, Ken, Zhou, Wei, Guo, Yi, Hu, Guofu, Chu, Jie, Xie, Fen, Li, Yiqing, Wang, Weici
• Format: Article
• Language: English
• Subjects: Angioplasty - adverse effects; Animals; Antioxidants - metabolism; Cell Movement - drug effects; Cell Proliferation - drug effects; Coronary Restenosis - etiology; Coronary Restenosis - metabolism; Coronary Restenosis - pathology; Hydrogen Sulfide - pharmacology; Hyperplasia; Inflammation - pathology; Male; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Oxidation-Reduction; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Tunica Intima - drug effects; Tunica Intima - pathology
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/1535370220961038

Restenosis after angioplasty of peripheral arteries is a clinical problem involving oxidative stress. Hydrogen sulfide (H S) participates in oxidative stress regulation and activates nuclear factor erythroid 2-related factor 2 (Nrf2). This study investigated the effect of H S and Nrf2 on restenosis-induced arterial injury. Using an rat model of restenosis, we investigated whether H S inhibits restenosis after percutaneous transluminal angioplasty (PTA) and the oxidative stress-related mechanisms implicated therein. The involvement of Nrf2 was explored using Nrf2-shRNA. Neointimal formation and the deposition of elastic fibers were assessed histologically. Inflammatory cytokine secretion and the expression of proteins associated with oxidative stress and inflammation were evaluated. The artery of rats subjected to restenosis showed increased arterial intimal thickness, with prominent elastic fiber deposition. Sodium hydrosulfide (NaHS), an H S donor, counteracted these changes . Restenosis caused a decrease in anti-oxidative stress signaling. This phenomenon was inhibited by NaHS, but Nrf2-shRNA counteracted the effects of NaHS. In terms of inflammation, inflammatory cytokines were upregulated, whereas NaHS suppressed the induced inflammatory reaction. Similarly, Nrf2 downregulation blocked the effect of NaHS. studies using aortic endothelial and vascular smooth muscle cells isolated from experimental animals showed consistent results as those of studies, and the participation of the nuclear factor-kappa B signaling pathway was demonstrated. Collectively, H S played a role in regulating post-PTA restenosis by alleviating oxidative stress, modulating anti-oxidant defense, and targeting Nrf2-related pathways via nuclear factor-kappa B signaling.