Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai 200032, China.
J Cell Biochem. 2011 Jan;112(1):256-64. doi: 10.1002/jcb.22923.
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.
动脉内皮细胞（AEC）对动脉粥样硬化因子的反应性明显大于静脉内皮细胞（VEC）。然而，这种现象的原因尚不清楚。鸡卵清蛋白上游启动子转录因子 II（COUP-TFII）在调节胚胎动静脉分化中起重要作用。因此，我们研究 COUP-TFII 是否与 AEC 和 VEC 之间这种不同的易感性有关。首先确认 COUP-TFII 在成人 VEC 中表达，但在 AEC 中不表达。通过 siRNA 策略，我们发现敲低 COUP-TFII 后，培养的人 VEC 中通常只存在于 AEC 中的 Jagged1 和 Notch1 的表达。为了进一步阐明 COUP-TFII 的作用，我们在转染 COUP-TFII siRNA 的 VEC 中进行了 DNA 微阵列，并随后用血管紧张素 II（AngII）刺激，并比较了涉及各种动脉粥样硬化相关途径的 112 个基因的表达谱。结果表明，在转染 COUP-TFII siRNA 的 VEC 中，AngII 刺激后致动脉粥样硬化基因的表达明显上调。此外，体外细胞功能测定表明，COUP-TFII 在 VEC 中的敲低不仅增加了基础水平，而且增加了 AngII 诱导的细胞黏附。这些结果表明，COUP-TFII 通过控制各种动脉粥样硬化相关分子的表达来抑制 VEC 对动脉粥样硬化的易感性。
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