Immunometabolic mechanisms and therapeutic perspectives in aortic dissection

Aortic dissection (AD) is a life-threatening cardiovascular disease with high morbidity and mortality. Its pathogenesis involves tearing of the aortic intima, degradation of the extracellular matrix (ECM), phenotypic transformation of vascular smooth muscle cells (VSMCs), and excessive inflammatory activation. However, effective therapeutic strategies to prevent AD progression are still lacking. Recent studies have revealed that immunometabolic mechanisms play a crucial role in the initiation and progression of AD. Inflammatory responses, particularly macrophage activation and secretion of matrix metalloproteinases (MMPs), accelerate aortic wall destruction. Meanwhile, metabolic disorders such as diabetes mellitus and dyslipidemia further increase the risk of AD by impairing VSMC function and promoting oxidative stress. Metabolic reprogramming of immune and vascular cells regulates inflammatory activation, oxidative stress, phenotypic switching, and extracellular matrix remodeling, thereby creating a self-amplifying immunometabolic network that increases aortic wall fragility and susceptibility to dissection. This review summarizes current advances in understanding the interplay between immune regulation and metabolic processes in AD. By elucidating the immunometabolic mechanisms underlying AD, we aim to provide new insights into its pathogenesis and identify potential molecular targets for the prevention, diagnosis, and treatment of this devastating disease.