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.
Keywords: Atherosclerotic lesion calcification; Endothelial cells; Endothelial-mesenchymal transition; Serine protease; Sex-determining region Y-box 2.
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