College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
Int J Mol Sci. 2022 Dec 22;24(1):172. doi: 10.3390/ijms24010172.
Inflammation is closely associated with progression of vascular remodeling. The NLRP3 inflammasome is the key molecule that promotes vascular remodeling via activation of vascular adventitia fibroblast (VAF) proliferation and differentiation. VAFs have a vital effect on vascular remodeling that could be improved using hydroxysafflower yellow A (HSYA). However, whether HSYA ameliorates vascular remodeling through inhibition of NLRP3 inflammasome activation has not been explored in detail. Here, we cultured primary VAFs and analyzed the migration of VAFs induced by angiotensin II (ANG II) to determine the potential effects and mechanism of HSYA on VAF migration. The results thereof showed that HSYA remarkably inhibited ANG II-induced VAF migration, NLRP3 inflammasome activation, and the TLR4/NF-κB signaling pathway in a dose-dependent manner. In addition, it is worth noting that LPS promoted ANG II-induced VAF migration and NLRP3 inflammasome assembly, which could be significantly reversed using HSYA. Moreover, HSYA could be used to inhibit NLRP3 inflammasome activation by promoting autophagy. In conclusion, HSYA could inhibit ANG II-induced VAF migration through autophagy activation and inhibition of NLRP3 inflammasome activation through the TLR4/NF-κB signaling pathway.
炎症与血管重构的进展密切相关。NLRP3 炎性体是通过激活血管外膜成纤维细胞（VAF）增殖和分化来促进血管重构的关键分子。VAF 对血管重构具有重要作用，而羟基红花黄色素 A（HSYA）可以改善这一作用。然而，HSYA 是否通过抑制 NLRP3 炎性体激活来改善血管重构尚未详细探讨。在这里，我们培养了原代 VAF，并分析了血管紧张素 II（ANG II）诱导的 VAF 迁移，以确定 HSYA 对 VAF 迁移的潜在作用和机制。结果表明，HSYA 显著抑制了 ANG II 诱导的 VAF 迁移、NLRP3 炎性体激活和 TLR4/NF-κB 信号通路，呈剂量依赖性。此外，值得注意的是，LPS 促进了 ANG II 诱导的 VAF 迁移和 NLRP3 炎性体组装，而 HSYA 可以显著逆转这一作用。此外，HSYA 可以通过促进自噬来抑制 NLRP3 炎性体的激活。总之，HSYA 可以通过激活自噬和抑制 TLR4/NF-κB 信号通路来抑制 ANG II 诱导的 VAF 迁移。
