The morphological and molecular mechanisms of epithelial/endothelial-to-mesenchymal transition and its involvement in atherosclerosis.

Cell transdifferentiation occurs during cardiovascular development or remodeling either as a pathologic feature in the progression of disease or as a response to injury. Endothelial-to-Mesenchymal Transition (EndMT) is a process that is classified as a specialized form of Epithelial-to-Mesenchymal Transition (EMT), in which epithelial cells lose their epithelial characteristics and gain a mesenchymal phenotype. During transdifferentiation, cells lose both cell-cell contacts and their attachment to the basement membrane. Subsequently, the shape of the cells changes from a cuboidal to an elongated shape. A rearrangement of actin filaments facilitates the cells to become motile and prime their migration into the underlying tissue. EMT is a key process during embryonic development, wound healing and tissue regeneration, but has also been implicated in pathophysiological processes, such organ fibrosis and tumor metastases. EndMT has been associated with additional pathophysiological processes in cardiovascular related diseases, including atherosclerosis. Recent studies prove a significant role for EndMT in the progression and destabilization of atherosclerotic plaques, as a consequence of EndMT-derived fibroblast infiltration and the increased secretion of matrix metalloproteinase respectively. In this review we will discuss the essential molecular and morphological mechanisms of EMT and EndMT, along with their common denominators and key differences. Finally, we will discuss the role of EMT/EndMT in developmental and pathophysiological processes, focusing on the potential role of EndMT in atherosclerosis in more depth.