Asprosin promotes vascular inflammation via TLR4-NFκB-mediated NLRP3 inflammasome activation in hypertension
Rui Ge,
Jun-Liu Chen,
Fen Zheng,
Shu-Min Yin,
Min Dai,
Yi-Ming Wang,
Qi Chen,
Yue-Hua Li,
Guo-Qing Zhu,
Ai-Dong Chen
Affiliations
Rui Ge
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Jun-Liu Chen
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Fen Zheng
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Shu-Min Yin
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Min Dai
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Yi-Ming Wang
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Qi Chen
Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Yue-Hua Li
Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Guo-Qing Zhu
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Corresponding author. Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Ai-Dong Chen
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Corresponding author.
Objective: and design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. Methods: 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. Results: 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. Conclusions: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.
