RGFP966 inhibits palmitic acid induced VSMCs phenotypic transition by targeting ATGL.

IF 3.9 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-01-28 DOI:10.1016/j.bbalip.2025.159597

Siyi Zhang, Fangqin Nie, Youjie Zeng, Zhousheng Yang, Wenmin Song, Xin Yan, Zizhao Tang, Yangxia Fu, Ren Guo

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引用次数: 0

Abstract

Background: The phenotypic switch of vascular smooth muscle cells (VSMCs) underlies the pathology of many cardiovascular diseases. Histone deacetylase 3 (HDAC3) is reported to upregulate in several cardiovascular diseases. RGFP966 is a highly selective HDAC3 inhibitor. This study aimed to explore the effects of RGFP966 on the phenotypic switch of VSMCs.

Method: First, we conducted an analysis of HDAC3 expression utilizing pertinent Gene Expression Omnibus (GEO) datasets. Then CCK-8, Edu, and wound healing assays were used to explore the effects of RGFP966 on the proliferation and migration of VSMCs and potential mechanisms at the cellular level.

Results: Our results showed that palmitic acid (PA) induced the accumulation of lipid droplets in VSMCs, downregulated Adipose triglyceride lipase (ATGL), and increased VSMC viability and migration, which were significantly reversed by RGFP966. Additionally, siRNA targeting ATGL dramatically enhanced the VSMCs injury induced by PA. The autophagy inhibitor 3-Methyladenine (3-MA) partially reversed the decreased ATGL expression caused by PA. Furthermore, the p-mTOR/mTOR ratio decreased under PA induction and rebounded after administration of RGFP966.

Conclusion: RGFP966 has a protective effect against VSMCs phenotype transitions, potentially related to the regulation of ATGL.

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来源期刊

Biochimica et biophysica acta. Molecular and cell biology of lipids 生物-生化与分子生物学

CiteScore

11.00

自引率

2.10%

发文量

109

审稿时长

53 days

期刊介绍： BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.