Asprosin aggravates atherosclerosis via regulating the phenotype transformation of vascular smooth muscle cells

Yu Zhao; Zhengkai Wang; Yi Chen; Min Feng; Xinxin Liu; Huan Chen; Nannan Wang; Zhiqi Wang; Shifeng Cao; Jing Ren; Xue Liu; Yixiu Zhao; Yan Zhang

doi:10.1016/j.ijbiomac.2024.131868

Asprosin aggravates atherosclerosis via regulating the phenotype transformation of vascular smooth muscle cells

Int J Biol Macromol. 2024 Apr 25;268(Pt 2):131868. doi: 10.1016/j.ijbiomac.2024.131868. Online ahead of print.

Authors

Yu Zhao¹, Zhengkai Wang², Yi Chen², Min Feng², Xinxin Liu², Huan Chen², Nannan Wang², Zhiqi Wang², Shifeng Cao², Jing Ren², Xue Liu², Yixiu Zhao³, Yan Zhang⁴

Affiliations

¹ State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China; Department of Pathophysiology, Province Key Laboratory of Medicine-Food Homologous Resources and Prevention and Treatment of Metabolic Diseases, Basic Medical College, Qiqihar Medical University, Qiqihar 161000, China.
² State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
³ State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China. Electronic address: zhaoyixiu520@126.com.
⁴ State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, State Key Labratoray-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China. Electronic address: zhangyan@ems.hrbmu.edu.cn.

PMID: 38677690
DOI: 10.1016/j.ijbiomac.2024.131868

Abstract

Phenotype transformation of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis. Asprosin is a newly discovered adipokine, which is critical in regulating metabolism. However, the relationship between asprosin and phenotype transformation of VSMCs in atherosclerosis remains unclear. The aim of this study is to investigate whether asprosin affects the progression of atherosclerosis by inducing phenotype transformation of VSMCs. We established an atherosclerosis model in ApoE^-/- mice and administered asprosin recombinant protein and asprosin antibody to mice. Knocking down asprosin was also as an intervention. Interestingly, we found a correlation between asprosin levels and atherosclerosis. Asprosin promoted plaque formation and phenotype transformation of VSMCs. While, Asp^KD or asprosin antibody reduced the plaque lesion and suppressed vascular stiffness in ApoE^-/- mice. Mechanistically, asprosin induced phenotype transformation of MOVAs by binding to GPR54, leading to Gαq/11 recruitment and activation of the PLC-PKC-ERK1/2-STAT3 signaling pathway. Si GPR54 or GPR54 antagonist partially inhibited the action of asprosin in MOVAs. Mutant GPR54-(267, 307) residue cancelled the binding of asprosin and GPR54. In summary, this study confirmed asprosin activated GPR54/Gαq/11-dependent ERK1/2-STAT3 signaling pathway, thereby promoting VSMCs phenotype transformation and aggravating atherosclerosis, thus providing a new target for the treatment of atherosclerosis.

Keywords: Asprosin; Atherosclerosis; GPR54 signaling; VSMCs phenotype transformation.