Liraglutide blocks the proliferation, migration and phenotypic switching of Homocysteine (Hcy)-induced vascular smooth muscle cells (VSMCs) by suppressing proprotein convertase subtilisin kexin9 (PCSK9)/ low-density lipoprotein receptor (LDLR)

Bioengineered

Yilei Wang¹  Xinyu Zhang¹  Xiaohong Niu²  Ming Feng³  Jingquan Ji⁴ 

[1] Department of Basic Medicine, Changzhi Medical College, Changzhi, Shanxi, Chin;Department of Endocrinology, The Heji Affiliated Hospital of Changzhi Medical College, Changzhi, Shanxi, Chin;Department of Neurosurgery,Changzhi People’s Hospital, Changzhi, Shanxi, Chin;Department of Pathophysiology, Changzhi Medical College, Changzhi, Shanxi, Chin;

关键词: Liraglutide;    PCSK9;    LDLR;    proliferation;    migration;   

DOI  :  10.1080/21655979.2021.1982304

来源: Taylor & Francis

【 摘 要 】

Liraglutide, a glucagon-like peptide 1 (GLP1) receptor agonist, is known to inhibit the atherosclerosis of apoE mice and suppress the cellular behaviors of VSMCs induced by AngII. This study aimed to explore whether liraglutide can reduce the proliferation, invasion and phenotypic transformation of VSMCs induced by Hcy and the underlying mechanism. Hcy was used to induce the proliferation of VSMCs, and liraglutide was then used to expose the cells for assessing cell proliferation. Afterward, the cell migration and phenotypic switch were evaluated to observe the effects of liraglutide. Meanwhile, the expression of PCSK9 and LDLR was detected. After overexpressing PCSK9, the changes in proliferation, cell migration and phenotypic switch were estimated again. Hcy promoted cell proliferation of VSMCs, whereas liraglutide blocked the proliferation, migration and phenotypic switch of Hcy-induced VSMCs. Furthermore, the expression of PCSK9 was downregulated and LDLR expression was upregulated after liraglutide administration in Hcy-induced VSMCs. After overexpressing PCSK9, the proliferation, migration and phenotypic switch of Hcy-induced VSMCs were enhanced. Liraglutide blocked the proliferation, migration and phenotypic switching of Hcy-induced VSMCs by suppressing PCSK9/LDLR. This finding provided the basis for the future application of liraglutide as an effective drug for therapeutic strategy in targeting AS.

【 授权许可】

CC BY