SNAI2/SLUG: a key regulator of endothelial-to-mesenchymal transition and vascular remodeling in cardiovascular diseases

Abstract

Snail family transcriptional repressor 2 (SNAI2), also known as SLUG, is a canonical driver of epithelial-mesenchymal transition (EMT). While its oncogenic roles are well-established, emerging evidence underscores its pivotal involvement in cardiovascular diseases (CVDs). This review systematically summarizes the multifaceted functions of SNAI2 in the cardiovascular system, highlighting its role in mediating endothelial-to-mesenchymal transition (EndMT) and vascular smooth muscle cell (VSMC) phenotypic reprogramming. We detail the involvement of SNAI2 across a spectrum of pathologies, including atherosclerosis, aortic aneurysm, valvular heart disease, myocardial fibrosis, and pulmonary arterial hypertension. By acting as a critical nexus in signaling networks such as TGF-β, Notch, and Wnt, SNAI2 regulates cellular fate and extracellular matrix remodeling under pathological stress. Finally, we discuss the potential of SNAI2 as a diagnostic biomarker and a novel therapeutic target, offering prospective insights for the clinical management of CVDs.