Endothelial-mesenchymal transition in atherosclerotic lesion calcification.
Endothelial-mesenchymal transitions (EndMTs) in endothelial cells (ECs) contribute to vascular disease.



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



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.



Together, our data suggest that EndMTs contribute to atherosclerotic lesion calcification.
Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA; The Molecular Biology Institute at UCLA, Los Angeles, CA 90095-1570, USA. Electronic address: kbostrom@mednet.ucla.edu.
Kristina I
KI
Boström
Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA.
Jiayi
J
Yao
Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA.
Pierre J
PJ
Guihard
Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA.
Ana M
AM
Blazquez-Medela
Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA; Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA 90095, USA. Electronic address: yyao@mednet.ucla.edu.
Yucheng
Y
Yao
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood*; D002114:Calcinosis / Q000097:blood*; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D051379:Mice; D000074085:Mice, Knockout, ApoE; D058226:Plaque, Atherosclerotic / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D015854:Up-Regulation
D016207:Cytokines; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D002784:Cholesterol; D012697:Serine Endopeptidases
Atherosclerotic lesion calcification; Endothelial cells; Endothelial-mesenchymal transition; Serine protease; Sex-determining region Y-box 2