Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies

The modification of endothelial cells (ECs) biological function under pathogenic conditions leads to the expression of mesenchymal stromal cells (MSCs) markers, defined as endothelial-to-mesenchymal transition (EndMT). Invisible in onset and slow in progression, atherosclerosis (AS) is a potential contributor to various atherosclerotic cardiovascular diseases (ASCVD). By triggering AS, EndMT, the "initiator" of AS, induces the progression of ASCVD such as coronary atherosclerotic heart disease (CHD) and ischemic cerebrovascular disease (ICD), with serious clinical complications such as myocardial infarction (MI) and stroke. In-depth research of the pathomechanisms of EndMT and identification of potential targeted therapeutic strategies hold considerable research value for the prevention and treatment of ASCVD-associated with delayed EndMT. Although previous studies have progressively unraveled the complexity of EndMT and its pathogenicity triggered by alterations in vascular microenvironmental factors, systematic descriptions of the most recent pathogenic roles of EndMT in the progression of AS, targeted therapeutic strategies, and their future research directions are scarce.