SIRT3 Represses Vascular Remodeling via Reducing Mitochondrial Ac-CoA Accumulation in Vascular Smooth Muscle Cells

作者：Mei You, Bowen Wang, Li Li, Min Liu, Lijuan Wang, Tingbing Cao, Qing Zhou, Aidi Mou, Hongya Wang, Min Sun, Zongshi Lu, Zhiming Zhu, Zhencheng Yan, Peng Gao · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2025 · DOI：10.1161/atvbaha.125.322428 · 被引用次数：11 · 研究领域：Sirtuins and Resveratrol in Medicine、Mitochondrial Function and Pathology、Nuts composition and effects

BACKGROUND: Vascular remodeling characterized by vascular smooth muscle cell (VSMC) phenotypic switching is a key pathological process leading to numerous cardiovascular diseases, often accompanied by a decrease in mitochondrial oxidative phosphorylation. However, whether VSMC mitochondrial homeostasis plays a central role in vascular remodeling remains elusive. In this study, we investigated the role of SIRT3 (sirtuin 3), a deacetylase that maintains mitochondrial homeostasis, in vascular remodeling. METHODS: We established a VSMC-specific SIRT3 knockout mouse and a VSMC-specific SIRT3 overexpression mouse. Mice were infused with Ang II (angiotensin II) to establish the conventional abdominal aortic aneurysm model and underwent carotid artery ligation to establish the neointima formation model to investigate the role of SIRT3 in vascular remodeling. In vitro, quiescent-state VSMCs were stimulated with PDGF-BB (platelet-derived growth factor type BB) to investigate the direct role of SIRT3 in VSMC phenotypic switching, and the detailed mechanisms were investigated. RESULTS: The expression and activity of SIRT3 were decreased in the aortas from mice with Ang II–induced abdominal aortic aneurysm or ligation-induced neointima formation. VSMC-specific knockout of SIRT3 exacerbated vascular remodeling, whereas overexpression or activation of SIRT3 in VSMCs displayed therapeutic effect. Moreover, the reduction of SIRT3 was shown to increase the expression level of KLF4 (Kruppel-lik...