Emergency Department.
Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University.
J Hypertens. 2024 Aug 1;42(8):1427-1439. doi: 10.1097/HJH.0000000000003751. Epub 2024 Apr 22.
Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension.
VSMCs were obtained from the aortic media of 8-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR.
Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.
血管平滑肌细胞（VSMC）的增殖和迁移导致血管重构。天门冬素是一种新发现的蛋白激素，参与代谢性疾病。关于天门冬素在心血管疾病中的作用知之甚少。本研究主要关注天门冬素在高血压大鼠模型中对 VSMC 增殖和迁移以及血管重构的作用和机制。
从 8 周龄雄性 Wistar-Kyoto 大鼠（WKY）和自发性高血压大鼠（SHR）的主动脉中层获得 VSMC。SHR 的 VSMC 中天冬素上调。在体外研究中，天门冬素促进了 WKY 和 SHR 的 VSMC 增殖和迁移，并增加了烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）活性、NOX1/2/4 蛋白表达和超氧化物产生。敲低天冬素抑制了 SHR 的 VSMC 增殖、迁移、NOX 活性、NOX1/2 表达和超氧化物产生。天冬素促进 VSMC 增殖和迁移的作用不受过氧化氢清除剂的影响，但被超氧化物清除剂、选择性 NOX1 或 NOX2 抑制剂减弱。SHR 中 Toll 样受体 4（TLR4）上调，TLR4 敲低抑制了 WKY 和 SHR 的 VSMC 中天冬素过表达诱导的增殖、迁移和氧化应激。SHR 的动脉中天冬素上调，体内敲低天冬素不仅减轻了主动脉和肠系膜动脉的氧化应激和血管重构，还导致 SHR 随后持续的降压作用。
天门冬素通过 NOX 介导的超氧化物产生促进 VSMC 增殖和迁移。内源性天冬素表达的抑制减弱了 SHR 的 VSMC 增殖和迁移以及血管重构。
