Endothelial to Mesenchymal Transition: An Insight in Atherosclerosis

Abstract

Atherosclerosis is a fundamental disease of the cardiovascular system that leads to high morbidity and mortality worldwide. The endothelium is the first protective barrier in atherosclerosis. Endothelial cells have the potential to be transformed into mesenchymal cells, in a process termed endothelial to mesenchymal transition (EndMT). On the one hand, EndMT is known to contribute to atherosclerosis by inducing a number of phenotypes ranging from endothelial cell dysfunction to plaque formation. On the other hand, risk factors for atherosclerosis can lead to EndMT. A substantial body of evidence has suggested that EndMT induces the development of atherosclerosis; therefore, a deeper understanding of the molecular mechanisms underlying EndMT in atherosclerosis might provide insights to reverse this condition.

Keywords: EndMT-associated marker; atherosclerosis; endothelial to mesenchymal transition; plasticity of endothelial cells; regulating mechanisms.

Figure 1

Processes inducing EndMT in atherosclerosis. Factors that can lead to EndMT include several inflammatory cytokines, ox-LDL, nicotine, and shear stress. The transition from endothelial cells to mesenchymal cells (e.g., fibroblasts and smooth muscle cells) is accompanied by downregulation of endothelial markers and upregulation of mesenchymal markers.

Figure 2

Signaling pathways involved in EndMT in atherosclerosis. EndMT related transcription factors such as Snail, Slug, ZEB, TWIST, and FoxC2 are governed by upstream signalings including BMP, TGF-β, FGF, and Notch, which in turn regulate endothelial and mesenchymal gene expression, ultimately inducing EndMT.