Pro‐Atherosclerotic Effects of Osteopontin Is Contributed to Promoting Foam Cell Formation Derived From VSMCs by Inhibiting Cholesterol Efflux

作者：Wentao Liu, Yuan Wang, Chen Liu, Bowei Shi, Xiaowei Xiong, Sheng Chen, Qian-Qian Huang, Qian-Qian Huang, Li Wang, Guohua Zeng, Qiren Huang, Qiren Huang · 发表于：The FASEB Journal · 年份：2025 · DOI：10.1096/fj.202403104rr · 被引用次数：3 · 研究领域：Bone and Dental Protein Studies、Connective tissue disorders research、Digestive system and related health

ABSTRACT Atherosclerosis (AS) is the primary pathological basis of many cardiovascular diseases, and the formation of foam cells plays a critical role in the progression of AS. Increasing evidence shows that a considerable proportion of foam cells derive from vascular smooth muscle cells (VSMCs) in atherosclerotic plaques. Osteopontin (OPN), a glycosylated protein secreted by cells, is supposed to promote the development of AS. However, the underlying mechanisms of OPN contributing to the AS progression remain unclear. Therefore, the purpose of the study is to investigate the effects and mechanisms of OPN on VSMC‐foaming and AS. Mouse AS model was established by feeding ApoE −/− mice with high fat diet (HFD), and the foam cell model of murine aortic vascular smooth muscle cells (MOVAS) was induced with Ox‐LDL. During modeling, both ApoE −/− mice and MOVAS were infected with mouse recombinant adenoviruses expressing OPN (Ad‐OPN). Our results show that OPN aggravates vascular smooth muscle dysfunction and AS in the ApoE −/− mice fed with HFD. Besides, OPN reduces cholesterol efflux and further promotes the formation of VSMC‐derived foam cells by decreasing the expressions of ABCA1 and ABCG1. Furthermore, OPN inhibits the phosphorylation of p38MAPK through binding to its membrane receptor CD44, thereby reducing the expressions of LXRα, ABCA1, and ABCG1. Our results demonstrate that OPN reduces the expression of cholesterol transporters ABCA1 and ABCG1 and promotes the formation ...