Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: Cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress
Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: Cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress
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DOI：
10.1073/pnas.93.19.10417
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发表时间：
1996-09-17
影响因子：
11.1
通讯作者：
Gimbrone, MA
中科院分区：
文献类型：
--
作者：
Topper, JN;Cai, JX;Gimbrone, MA
早期动脉粥样硬化病变发展的地形图模式，强烈建议参与其发病机制的血流动力学力量。我们假设某些内皮基因对不同的流体机械刺激表现出不同的反应性，它们可能通过在动脉壁内局部水平上调节全身性危险因素的影响而参与动脉粥样硬化的发生过程。使用培养的人内皮细胞的差异显示策略已经鉴定了两种基因，锰超氧化物歧化酶和环氧合酶-2，其通过稳定层流剪切应力（LSS）表现出选择性和持续的上调。湍流剪切应力，非层流流体机械刺激，不诱导这些基因，内皮形式的一氧化氮合酶也表现出类似的LSS选择性诱导模式。因此，三个基因与潜在的动脉粥样硬化保护（抗氧化剂，抗血栓形成，抗粘附）活动表现出不同的流体机械刺激的差异反应，提供了一个可能的机制之间的联系内皮基因表达和动脉粥样硬化形成的早期事件。这些和其他LSS反应基因的活性可能对动脉粥样硬化的发病机制和预防具有重要意义。
Early atherosclerotic lesions develop in a topographical pattern that strongly suggests involvement of hemodynamic forces in their pathogenesis. We hypothesized that certain endothelial genes, which exhibit differential responsiveness to distinct fluid mechanical stimuli, may participate in the atherogenic process by modulating, on a local level within the arterial wall, the effects of systemic risk factors, A differential display strategy using cultured human endothelial cells has identified two genes, manganese superoxide dismutase and cyclooxygenase-2, that exhibit selective and sustained up-regulation by steady laminar shear stress (LSS). Turbulent shear stress, a nonlaminar fluid mechanical stimulus, does not induce these genes, The endothelial form of nitric oxide synthase also demonstrates a similar LSS-selective pattern of induction. Thus, three genes with potential atheroprotective (antioxidant, antithrombotic, and antiadhesive) activities manifest a differential response to distinct fluid mechanical stimuli, providing a possible mechanistic link between endothelial gene expression and early events in atherogenesis. The activities of these and other LSS-responsive genes may have important implications for the pathogenesis and prevention of atherosclerosis.