UNASSIGNED: Primary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), NLRP3-/- and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo.
UNASSIGNED: Asprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1β production, proliferation and migration were attenuated in NLRP3-/- VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling.
UNASSIGNED: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.
■从动物的主动脉获得原代血管平滑肌细胞(VSMC),包括自发性高血压大鼠(SHR),Wistar-Kyoto大鼠(WKY),NLRP3-/-和野生型小鼠。在体外VSMC中进行了研究,以及体内的WKY和SHR。
■在SHR的VSMC和动脉中膜中,Asprosin表达上调。Asprosin过表达通过Toll样受体4(TLR4)促进NLRP3炎性体激活,在VSMCs中伴有NFκB信号通路的激活。外源性反胰岛素蛋白在促进NLRP3炎性体激活中显示出相似的作用。抑制SHRVSMC中NLRP3炎性体和p65-NFκB的激活。NLRP3抑制剂MCC950或NFκB抑制剂BAY11-7082减弱了asprosin引起的VSMC增殖和迁移。天门冬氨酸诱导的白细胞介素-1β的产生,NLRP3-/-VSMC的增殖和迁移减弱。SHR颈总动脉中局部的asprosin敲除减轻了炎症和血管重塑。
■Asprosin通过TLR4-NFκB途径促进VSMC中NLRP3炎性体的激活,从而刺激VSMC增殖,迁移,和SHR的血管重塑。