National Center for Cardiovascular Research, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Curr Opin Lipidol. 2012 Oct;23(5):446-52. doi: 10.1097/MOL.0b013e328357e837.
Differences in local blood flow patterns along the endothelium may trigger abnormal vascular responses which can have profound pathophysiological consequences. While endothelial cells exposed to laminar blood flow (high shear stress) are protected from atherosclerosis formation, turbulent or disturbed blood flow, which occurs at bends and bifurcations of blood vessels, facilitates atherosclerosis formation. Here, we will highlight the endothelial cell mechanisms involved in detecting shear stress and their translation into downstream biochemical signals.
Prior evidence supports a role for integrins as mechanotransducers in the endothelium by promoting phosphorylation of different targets through the activation of focal adhesion kinase. Our recent findings show that integrins contact integrin-linked kinase and regulate vasomotor responses by an endothelial nitric oxide synthase-dependent mechanism, which stabilizes the production of vasoactive factor nitric oxide. In addition, different structures of endothelial cells, mainly primary cilia, are investigated, as they can explain the differential responses to laminar versus disturbed flow.
The discovery of a connection between endothelial cell structures such as cilia, integrin, extracellular matrix, and signaling events opens today a new chapter in our understanding of the molecular mechanisms regulating vascular responses to the changes in flow.
沿着内皮细胞的局部血流模式的差异可能引发异常的血管反应，这可能产生深远的病理生理后果。虽然暴露于层流（高剪切应力）的内皮细胞免受动脉粥样硬化形成的影响，但在血管弯曲和分叉处发生的湍流或紊乱血流促进了动脉粥样硬化的形成。在这里，我们将重点介绍内皮细胞检测剪切应力的机制及其转化为下游生化信号的机制。
先前的证据支持整合素作为内皮细胞中的机械转导物的作用，通过激活粘着斑激酶促进不同靶标的磷酸化。我们最近的发现表明，整合素与整合素连接激酶接触，并通过内皮型一氧化氮合酶依赖的机制调节血管舒缩反应，该机制稳定血管活性因子一氧化氮的产生。此外，还研究了内皮细胞的不同结构，主要是初级纤毛，因为它们可以解释对层流与紊乱流的不同反应。
内皮细胞结构（如纤毛、整合素、细胞外基质和信号事件）之间连接的发现，为我们理解调节血管对血流变化的反应的分子机制开辟了新篇章。
