Endothelial to mesenchymal transition: a central mechanism in diabetes-induced vascular pathology

Diabetes mellitus is a major global health concern associated with microand macrovascular complications. Among the diverse mechanisms that contribute to vascular dysfunction in diabetes, endothelial to mesenchymal transition (EndMT) has emerged as a key pathological process. EndMT involves the loss of endothelial cell characteristics and the acquisition of mesenchymal features, resulting in impaired endothelial function, increased fibrosis, and inflammation. In addition to findings from preclinical models, recent human studies support the clinical relevance of End-MT. This review summarizes the molecular mechanisms governing EndMT, including key signaling pathways such as TGF-β, Notch, and Wnt, and examines how environmental, metabolic, and inflammatory cues influence this process. Furthermore, we discuss the maladaptive role of EndMT in diabetic complications, including nephropathy, retinopathy, atherosclerosis, and impaired wound healing, highlighting recent advances in anti-EndMT therapies and the clinical implications. Understanding the mechanisms of EndMT in the diabetic milieu may reveal novel therapeutic targets for preventing or reversing diabetic vascular diseases.