The roles of the COXs in normal physiology and in pathological conditions

这些研究的主要目的是阐明COX-1和COX-2在正常生理和各种病理状态中的个体作用。具体来说，实验室的工作重点是使用COX-2缺陷小鼠ES细胞和COX特异性抑制剂来研究COX-2在内皮细胞发育和动脉瘤形成中的作用。内皮细胞分化通过CD-31染色细胞样结构的出现和Western分析VEGF受体和COX-2的出现进行免疫组织化学测定。我们的研究表明，缺乏COX-2可以抑制小鼠胚胎干细胞向内皮样细胞的体外分化。然而，COX-2选择性抑制剂的研究表明，COX-2抑制剂甚至在COX-2-/- ES细胞中也能阻断内皮样细胞的发育，这表明COX-2独立的机制起作用。

The major goals of these studies are to elucidate the individual roles of COX-1 and COX-2 in normal physiology and in various pathological states. Specifically, effort within the laboratory has focused on using COX-2 deficient mouse ES cells and COX specific inhibitors to study the roles of COX-2 in endothelial cell development and aneurysm formation. Endothelial cell ifferentiation was measured immunohistochemically by the appearance of CD-31 staining cord like structures of cells and the appearance of VEGF receptors and COX-2 on Western analysis. Our studies indicated that the deficiency of COX-2 inhibited mouse ES cell differentiation into endothelial-like cells in vitro. However, studies with COX-2 selective inhibitors have indicated that the COX-2 inhibitors blocked endothelial-like cell development even in COX-2-/- ES cells, suggesting that a COX-2 independent mechanism was responsible. In addition, a mouse model to study the contributions of COX-2 to aneurysm formation is being developed and initial studies indicate that COX-2 deficiency attenuates inflammatory responses in the mouse heart and abdominal vasculature. Also, collaborative studies have demonstrated that COX-2 deficiency increased inflammatory responses in the mouse brain.