COUP-TFII switches responses of venous endothelium to atherosclerotic factors through controlling the profile of various inherent genes expression.
Endothelial cells of arteries (AEC) have a strikingly greater responsiveness to atherosclerosis factors than venous endothelial cells (VEC). However, the reasons for this phenomenon remain unclear. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) plays an important role in regulating embryonic arterial-venous differentiation. We therefore investigate whether COUP-TFII is related to this different susceptibility between AEC and VEC. It is first confirmed that COUP-TFII is expressed in VEC but not in AEC in the adult. Using a siRNA strategy, we identified the expression of Jagged1 and Notch1 in cultured human VEC, which usually exist only in AEC, after knocking down of COUP-TFII. To further elucidate the role of COUP-TFII, we performed DNA microarrays in VEC transfected with the siRNA of COUP-TFII and subsequently stimulated with angiotensin II (AngII) and compared the expression profiles of 112 genes involved in various atherosclerosis-related pathways. The results indicated that expression of atherogenic genes was significantly upregulated after AngII stimulation in VEC transfected with COUP-TFII siRNA. Moreover, in vitro cell functional assay showed that knockdown of COUP-TFII in VEC increased not only basal but also AngII-induced cell adhesions. These results demonstrate that COUP-TFII suppresses the susceptibility of VEC to atherosclerosis through controlling the expression of various atherosclerosis-related molecules.
Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai 200032, China.
Xiaojing
X
Wu
Yunzeng
Y
Zou
Yanyan
Y
Liang
Qi
Q
Zhou
Hui
H
Gong
Aijun
A
Sun
Lingyan
L
Yuan
Keqiang
K
Wang
Junbo
J
Ge
D000818:Animals; D051837:COUP Transcription Factor II / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D014680:Veins / Q000166:cytology*
D051837:COUP Transcription Factor II; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins