Endothelial-mesenchymal transition in atherosclerotic lesion calcification

•Endothelial-mesenchymal transitions (EndMTs) in atherosclerotic lesions contribute to calcification.•Stem cell and mesenchymal markers, including Sox2, are upregulated in aortic endothelial cells (ECs) of fat-fed ApoE−/− mice.•Limiting Sox2 decreases the stem cell and mesenchymal markers and calcification in ApoE −/− aortas.•A complex of serine proteases is upregulated in ApoE −/− aortic ECs.•Blockade of these proteases reduces expression of Sox2 and atherosclerotic lesion calcification.

Background and aimsEndothelial-mesenchymal transitions (EndMTs) in endothelial cells (ECs) contribute to vascular disease.MethodsWe used ApoE−/− mice fed a high-fat/high-cholesterol diet.ResultsWe 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.ConclusionsTogether, our data suggest that EndMTs contribute to atherosclerotic lesion calcification.