title: Venous Endothelial Marker COUP-TFII Regulates the Distinct Pathologic Potentials of Adult Arteries and Veins.
abstract: Arteries and veins have very different susceptibility to certain vascular diseases such as atherosclerosis and vascular calcification. The molecular mechanisms of these differences are not fully understood. In this study, we discovered that COUP-TFII, a transcription factor critical for establishing the venous identity during embryonic vascular development, also regulates the pathophysiological functions of adult blood vessels, especially those directly related to vascular diseases. Specifically, we found that suppression of COUP-TFII in venous ECs switched its phenotype toward pro-atherogenic by up-regulating the expression of inflammatory genes and down-regulating anti-thrombotic genes. ECs with COUP-TFII knockdown also readily undergo endothelial-to-mesenchymal transition (EndoMT) and subsequent osteogenic differentiation with dramatically increased osteogenic transcriptional program and calcium deposition. Consistently, over-expression of COUP-TFII led to the completely opposite effects. In vivo validation of these pro-atherogenic and osteogenic genes also demonstrates a broad consistent differential expression pattern in mouse aorta vs. vena cava ECs, which cannot be explained by the difference in hemodynamic flow. These data reveal phenotypic modulation by different levels of COUP-TFII in arterial and venous ECs, and suggest COUP-TFII may play an important role in the different susceptibilities of arteries and veins to vascular diseases such as atherosclerosis and vascular calcification.
authors.affiliation: School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China 430070.|Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cui
authors.affiliation: The Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Yao Wei
authors.initials: YW
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.|Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.|Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.|Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Dorsey
authors.affiliation: Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.affiliation: The Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Vincent
authors.affiliation: The Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA.
authors.forename: John
authors.initials: J
authors.lastname: Schwarz
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.|Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
authors.forename: Guohao
authors.initials: G
authors.lastname: Dai
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D051837:COUP Transcription Factor II / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D051379:Mice; D010012:Osteogenesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014680:Veins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051837:COUP Transcription Factor II; D014157:Transcription Factors