Mechanotransduction in vascular physiology and pathology

排列在血管上的内皮细胞由于血液流动而不断地受到诸如剪切应力之类的力的影响。这些力量不仅对血管发育至关重要，而且还调节血管生理和产后疾病。剪切应力由内皮表面表达的机械感受器感知，机械感受器将机械信号解码为生化信号级联，最终决定血管的表型和功能。我们最近发现了一种新的机械受体，它决定了血流紊乱区域动脉粥样硬化斑块的形成。我们现在建议使用跨学科的方法来解决这种机械受体在人类疾病中的相关性；其在生理反应中的相关性及其作用的分子机制。这项工作的完成不仅将定义基础科学和机械转导的基本原理，而且将为动脉粥样硬化和心血管疾病的转化研究和治疗开发开辟新的途径。

Endothelial cells that line blood vessels are constantly exposed to forces, such as shear stress, dueto the flowing blood. These forces are not only critical for vascular development, but also regulatevessel physiology and disease postnatally. Shear stress is sensed by mechanoreceptors expressedon endothelial surfaces which decode mechanical signals into biochemical signalling cascades thatwill ultimately define vessel phenotype and function. We have recently discovered a novelmechanoreceptor that dictates formation of atherosclerotic plaques in areas of disturbed flow. Wenow propose to use a cross-disciplinary approach to address the relevance of this mechanoreceptorin human disease; its relevance in physiological responses and its molecular mechanism of action.Completion of this work will not only define fundamental principles in basic science andmechanotransduction, but will opens up new avenues for translational research and therapeuticdevelopment against atherosclerosis and cardiovascular disease.