Induction of cyclooxygenase-2 in human saphenous vein and internal mammary artery
Induction of cyclooxygenase-2 in human saphenous vein and internal mammary artery
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DOI：
10.1161/01.atv.17.9.1644
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发表时间：
1997-09-01
影响因子：
8.7
通讯作者：
Mitchell, JA
中科院分区：
文献类型：
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作者：
BishopBailey, D;Pepper, JR;Mitchell, JA
在血管内，环氧合酶(COX)在内皮细胞中结构性表达(COX-1)，其产生的前列环素被认为有助于维持血管的完整性。最近，一种新的环氧合酶亚型COX-2被描述为COX-2，它是在物理损伤或暴露于促炎细胞因子后在动物动脉血管中诱导的。然而，COX-2在人血管中的诱导作用尚未明确。此外，动脉和静脉表达COX-2的相对能力尚未得到解决。因此，我们比较了从同一患者获得的人大隐静脉和乳内动脉段在有无白细胞介素1β的情况下，在器官培养后表达COX-2活性和mRNA的能力。用放射免疫法测定COX-2代谢物由乳内动脉和隐静脉释放的顺序如下：前列腺素E-2大于或等于前列环素血栓素A(2)。在培养液中加入IL-1β可增加隐静脉释放前列腺素，但不能增加乳内动脉释放前列腺素。然而，选择性COX-2抑制剂NS-398显著抑制这两种组织的前列环素释放。Northern印迹分析显示，新鲜制备的大鼠隐静脉和乳内动脉中未检测到COX-2mRNA。相反，在器官培养48h后，在乳内动脉和隐静脉中都检测到低水平的COX-2mRNA，这种作用被IL-1β大大增强。这些观察表明，COX-2在人类隐静脉和乳内动脉中被诱导，并提示这种情况可能发生在冠状动脉搭桥术后的人类身上。COX-2的诱导和随后前列环素的释放可能代表了一种内源性防御机制，以对抗外科手术准备搭桥过程中造成的内皮损伤。
Within vessels, cyclooxygenase (COX) is expressed constitutively (COX-1) in endothelial cells where its production of prostacyclin is thought to contribute to the maintenance of vascular integrity. Recently, a novel isoform of COX, COX-2, has been described that is induced in animal arterial vessels after physical damage or exposure to proinflammatory cytokines. However, induction of COX-2 in human vessels has not been characterized. Moreover, the relative ability of arteries and veins to express COX-2 has not been addressed. Thus, we have compared the ability of segments of human saphenous vein and internal mammary artery, obtained from the same patient, to express COX-2 activity and mRNA after organ culture in the presence and absence of interleukin-1 beta. COX-2 metabolites, measured by radioimmunoassay, were released by both the internal mammary artery and saphenous vein in the following rank order: prostaglandin E-2 greater than or equal to prostacyclin thromboxane A(2). Inclusion of interleukin-1 beta in the culture medium increased the release of prostanoids by the saphenous vein but not by the internal mammary artery. However, the selective COX-2 inhibitor NS-398 significantly attenuated prostacyclin release from both tissues. Northern blot analysis showed no detectable COX-2 mRNA in freshly prepared saphenous vein or internal mammary artery. In contrast, after 48 hours in organ culture, low levels of COX-2 mRNA were detected in both internal mammary artery and saphenous vein, an effect that was greatly increased by interleukin-1 beta. These observations show that COX-2 is induced in human saphenous vein and internal mammary artery and suggest that this may occur in humans after coronary artery bypass graft surgery. The induction of COX-2 and subsequent release of prostacyclin may represent an endogenous defense mechanism against endothelial damage incurred during surgical preparation of these vessels for bypass.