Abstract：
OBJECTIVE: 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.
RESULTS: 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.
CONCLUSIONS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：血管平滑肌细胞（VSMC）的增殖和迁移参与了血管重构。Asprosin,一种新发现的蛋白质激素，与代谢性疾病有关。人们对反前列腺素在心血管疾病中的作用知之甚少。本研究主要探讨了天门冬氨酸对VSMC增殖和迁移的作用及机制。高血压大鼠模型的血管重构。
结果：VSMC是从8周龄雄性Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）的主动脉培养基中获得的。Asprosin在SHR的VSMC中上调。对于体外研究，Asprosin促进VSMC增殖和WKY和SHR的迁移,和增加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。敲除反前列腺素抑制增殖，迁移,NOX活性,SHRVSMC中NOX1/2的表达和超氧化物的产生。促VSMC增殖和迁移的作用不受过氧化氢清除剂的影响，但是被超氧化物清除剂减毒，选择性NOX1或NOX2抑制剂。Toll样受体4（TLR4）在SHR中上调，TLR4敲低抑制反转录素过度表达诱导的增殖，WKY和SHRVSMCs的迁移和氧化应激。SHR动脉中的Asprosin上调，在体内敲除的同时,不仅减轻了主动脉和肠系膜动脉的氧化应激和血管重构,而且在SHR中也引起了持续的降压作用.
结论：Asprosin通过NOX介导的超氧化物产生促进VSMC增殖和迁移。抑制内源性反前列腺素表达减弱VSMC增殖和迁移，和SHR的血管重塑。
结果：VSMC是从8周龄雄性Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）的主动脉培养基中获得的。Asprosin在SHR的VSMC中上调。对于体外研究，Asprosin促进VSMC增殖和WKY和SHR的迁移,和增加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。敲除反前列腺素抑制增殖，迁移,NOX活性,SHRVSMC中NOX1/2的表达和超氧化物的产生。促VSMC增殖和迁移的作用不受过氧化氢清除剂的影响，但是被超氧化物清除剂减毒，选择性NOX1或NOX2抑制剂。Toll样受体4（TLR4）在SHR中上调，TLR4敲低抑制反转录素过度表达诱导的增殖，WKY和SHRVSMCs的迁移和氧化应激。SHR动脉中的Asprosin上调，在体内敲除的同时,不仅减轻了主动脉和肠系膜动脉的氧化应激和血管重构,而且在SHR中也引起了持续的降压作用.
结论：Asprosin通过NOX介导的超氧化物产生促进VSMC增殖和迁移。抑制内源性反前列腺素表达减弱VSMC增殖和迁移，和SHR的血管重塑。
