Vascular Smooth Muscle Cell Metabolic Disorders in the Occurrence and Development of Aortic Aneurysms and Dissections: Implications for Therapy
Yuqing Shi, Xiaoyan Xie, Yang Sun, Yanghui Chen, Guangzhi Chen
Abstract
Aortic aneurysm and dissection (AAD) represent a life-threatening aortic disorder, for which current treatment strategies rely predominantly on surgical interventions, with limited pharmacological options targeting the underlying pathophysiology. Vascular smooth muscle cell (VSMC) dysfunction constitutes a central pathological mechanism in the development and progression of AAD. This review outlines the association between VSMCs and AAD, covering their physiological functions and pathological alterations, including phenotypic switching, cell death, and VSMC-mediated extracellular matrix remodeling. It further discusses the impact of epigenetic modifications on VSMC core functions. Additionally, this review addresses normal energy metabolism pathways of VSMCs and the mechanisms of metabolic reprogramming, as well as abnormalities in amino acid metabolism, lipid metabolism, and other metabolic pathways. Signaling mechanisms related to AMPK activation and mitochondrial function are also highlighted. Currently, AAD management is dominated by surgical interventions, while pharmacological therapy remains limited to symptomatic control. Looking ahead, future research should focus on VSMC metabolism-related mechanisms to develop early prevention strategies and novel targeted therapeutics, thereby improving the current treatment landscape for AAD.