Energetic Decoding of VSMC Plasticity: Metabolic Reprogramming and Phenotypic Switching

Tingyu Yan, Qian Nie, Bo Xu, Xin Peng, Jiecan Zhuo
First Affiliated Hospital, Hengyang Medical School and University of South China.
China

Cardiovascular Drugs and Therapy
Cardiovasc Drugs Ther 2026;
DOI: 10.1007/s10557-026-07959-3

Abstract
Phenotypic switching of vascular smooth muscle cells (VSMCs) constitutes a pivotal event in the initiation and progression of various vascular diseases, including vascular calcification, atherosclerosis, aneurysm, and pulmonary arterial hypertension. The transition from a contractile to a synthetic phenotype is commonly characterized by increased proliferation, migration, and extracellular matrix synthesis, thus generating substantial bioenergetic demands. In recent years, accumulating evidence has indicated that metabolic reprogramming has emerged as a key regulatory dimension of VSMC plasticity. In this review, we systematically summarize the regulatory mechanisms by which metabolic reprogramming governs VSMC phenotypic switching, focusing mainly on glucose, lipid, and amino acid metabolism, while also discussing selected metabolite-derived signaling events and disease-context-specific metabolic patterns. We particularly emphasize how metabolic alterations collectively help shape VSMC fate through the integrated effects of energy supply, metabolic intermediates, and their associated signaling networks. Our aim is to establish a systematic theoretical framework linking metabolic reprogramming to VSMC phenotypic switching, thereby providing new insights into the mechanisms underlying vascular remodeling and laying a theoretical foundation for the development of metabolism-targeted therapeutic strategies.

Category
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Review Articles Concerning Pulmonary Vascular Disease

Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease

Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication

Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: No

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