The Contribution of Endothelial-Mesenchymal Transition to Atherosclerosis

Abstract

Atherosclerosis is a chronic progressive condition in which the wall of the artery develops abnormalities and causes thickening of the blood vessels. The development of atherosclerosis is a complex process characterized by vascular inflammation and the growth of atherosclerotic plaques that eventually lead to compromised blood flow. The endothelial to mesenchymal transition (EndMT) is a phenomenon whereby endothelial cells lose their endothelial properties and acquire a mesenchymal phenotype similar to myofibroblast and smooth muscle cells. This process is considered a key contributor to the development and, importantly, the progression of atherosclerosis. Thus, therapeutically targeting the EndMT will provide a broad strategy to attenuate the development of atherosclerosis. Here, we review our current knowledge of EndMT in atherosclerosis including several key pathways such as hypoxia, TGF-β signaling, inflammation, and environmental factors during the development of atherosclerosis. In addition, we discuss several transgenic mouse models for studying atherosclerosis. Taken together, rapidly accelerating knowledge and continued studies promise further progress in preventing this common chronic disease.

The Role of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease

“…In the normal physiological condition, this cell fate conversion is necessary to properly form the cardiac valves of the developing heart [ 33 ]. However, EndoMT recurs postnatally during the development of various cardiovascular diseases (CVDs), such as atherosclerosis, adult valve diseases, myocardial fibrosis, and pulmonary arterial hypertension (PAH) [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. In the EndoMT transitional process, endothelial cells progressively lose endothelial-specific markers and gain mesenchymal phenotypes [ 45 ].…”

Uncovering the heterogeneity and cell fate decisions of endothelial cells after myocardial infarction by single‐cell sequencing

“…Normally quiescent, ECs can acquire plasticity in response to disease, enabling them to adopt an angiogenic phenotype. A phenotypic switch from vascular ECs to mesenchymal cells, known as endothelial-to-mesenchymal transition (EndoMT), has been observed in multiple cardiovascular diseases [4,[10][11][12]. This transition involves a gradual loss of endothelial-specific markers, acquisition of a mesenchymal phenotype, downregulation of cell adhesion molecules, and upregulation of mesenchymal-specific factors.…”