Endothelial-mesenchymal transition in atherosclerotic lesion calcification.

Background And Aims: Endothelial-mesenchymal transitions (EndMTs) in endothelial cells (ECs) contribute to vascular disease.

Methods: We used ApoE mice fed a high-fat/high-cholesterol diet.

Results: We reported evidence of EndMT in atherosclerotic lesions contributing to calcification. Stem cell and mesenchymal markers, including sex-determining region Y-box 2 (Sox2), were upregulated in aortic ECs of fat-fed ApoE mice. Limiting Sox2 decreased marker expression and calcification in ApoE aortas. Furthermore, a complex of serine proteases was upregulated in ApoE aortic ECs. Blockade of these proteases reduced expression of Sox2 and atherosclerotic lesion calcification.

Conclusions: Together, our data suggest that EndMTs contribute to atherosclerotic lesion calcification.