Endothelial-to-mesenchymal transition (EndMT) in atherosclerosis: mechanisms, models and therapies

Abstract

Endothelial-to-mesenchymal transition (EndMT) has emerged as a key contributor to the development and progression of atherosclerotic cardiovascular disease. Driven by biomechanical, inflammatory, and metabolic cues within the vascular microenvironment, EndMT leads to the loss of endothelial identity and the acquisition of mesenchymal characteristics, thereby promoting vascular dysfunction and plaque progression. In this review, we present a comprehensive and up-to-date (as of April 15, 2026) overview of the molecular drivers and experimental models of EndMT in atherosclerosis, and critically evaluate current and emerging therapeutic strategies aimed at modulating this process. Furthermore, we emphasize the unresolved methodological challenges, which include the absence of standardized and quantitative approaches for EndMT detection, and the strong context dependency of existing experimental models. Emerging technologies, including genetic lineage tracing and single-cell transcriptomics, have revealed previously unrecognized cellular heterogeneity, context-dependent functional roles, and sex-specific EndMT signatures within human atherosclerotic plaques. Integrating recent advances in molecular biology, in vivo modeling, and translational research, this review provides a structured framework for understanding the multifaceted role of EndMT in atherosclerosis and outlines key challenges to be addressed to facilitate the translation of basic discoveries into clinical applications.