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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.