Asynchronous shear stress and circumferential strain reduces endothelial NO synthase and cyclooxygenase-2 but induces endothelin-1 gene expression in endothelial cells
Asynchronous shear stress and circumferential strain reduces endothelial NO synthase and cyclooxygenase-2 but induces endothelin-1 gene expression in endothelial cells
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DOI：
10.1161/01.atv.0000143855.85343.0e
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发表时间：
2004-11-01
影响因子：
8.7
通讯作者：
Tarbell, JM
中科院分区：
文献类型：
--
作者：
Dancu, MB;Berardi, DE;Tarbell, JM
目的——内皮源性血管活性药物NO、内皮素-1 （ET-1）和前列环素（PGI(2)）不仅调节血管张力，还影响动脉粥样硬化过程，包括平滑肌迁移和增殖，以及单核细胞和血小板粘附。复杂的血流动力学以机械因素周向应变和壁面剪切应力（应力相位角[SPA]）之间的时间相位角为特征，涉及易发生病理发展的区域，如动脉粥样硬化和内膜增生，在冠状动脉和外周动脉中，机械力是高度不同步的（SPA = - 180度）。我们检测了相对于正常血流动力学（SPA = 0度），非同步血流动力学（SPA = - 180度）对牛主动脉内皮细胞内皮NO合成酶（eNOS）、ET-1和环氧化酶-2 （COX-2）基因表达的影响。方法和结果-定量竞争性RT-PCR分析显示，与同步血流动力学（SPA = 0度）相比，异步血流动力学（SPA = - 180度）在基因表达水平上降低了eNOS产生（5和12小时）和COX-2产生（5小时），而ET-1表现出相反的趋势（5和12小时）。5和12小时后，NO、ET-1和PGI(2)的分泌随各自基因表达谱变化。综上所述，这些数据表明，高度不同步的机械力模式（SPA = - 180度）可以在基因表达水平上引发内皮细胞的促动脉粥样硬化血管活性反应，这表明了一种诱导心血管病理的新机制。
Objective - Endothelium-derived vasoactive agents NO, endothelin-1 (ET-1), and prostacyclin (PGI(2)) not only regulate vascular tone but also influence atherogenic processes, including smooth muscle migration and proliferation, as well as monocyte and platelet adhesion. Complex hemodynamics characterized by the temporal phase angle between mechanical factors circumferential strain and wall shear stress ( stress phase angle [ SPA]) have been implicated in regions prone to pathologic development, such as atherosclerosis and intimal hyperplasia, in coronary and peripheral arteries where the mechanical forces are highly asynchronous (SPA = - 180degrees). We determined the gene expression of endothelial NO synthase ( eNOS), ET-1, and cyclooxygenase-2 (COX-2) affected by asynchronous hemodynamics (SPA = - 180degrees) relative to normal hemodynamics ( SPA = 0degrees) in bovine aortic endothelial cells.Methods and Results - Quantitative competitive RT-PCR analysis showed that eNOS production ( at 5 and 12 hours) and COX-2 production ( at 5 hours) were reduced at the gene expression level by asynchronous hemodynamics (SPA = - 180degrees) compared with synchronous hemodynamics (SPA = 0degrees), whereas ET-1 exhibited an opposite trend ( at 5 and 12 hours). NO, ET-1, and PGI(2) secretion followed their respective gene expression profiles after 5 and 12 hours.Conclusion - Together, these data suggest that highly asynchronous mechanical force patterns ( SPA = - 180degrees) can elicit proatherogenic vasoactive responses in endothelial cells at the gene expression level, indicating a novel mechanism that induces cardiovascular pathology.