Angiogenesis Research Group, Centre for Cardiovascular Sciences, Medical School, University of Birmingham, Birmingham B15 2TT, UK.
Biochem Soc Trans. 2011 Dec;39(6):1633-8. doi: 10.1042/BST20110715.
EC (endothelial cell) responses to shear stress generated by vascular perfusion play an important role in circulatory homoeostasis, whereas abnormal responses are implicated in vascular diseases such as hypertension and atherosclerosis. ECs subjected to high shear stress in vitro alter their morphology, function and gene expression. The molecular basis for mechanotransduction of a shear stress signal, and the identity of the sensing mechanisms, remain unclear with many candidates under investigation. Translating these findings in vivo has proved difficult. The role of VEGF (vascular endothelial growth factor) flow-dependent nitric oxide release in remodelling skeletal muscle microcirculation is established for elevated (activity, dilatation) and reduced (overload, ischaemia) shear stress, although their temporal relationship to angiogenesis varies. It is clear that growth factor levels may offer only a permissive environment, and alteration of receptor levels may be a viable therapeutic target. Angiogenesis in vivo appears to be a graded phenomenon, and capillary regression on withdrawal of stimulus may be rapid. Combinations of physiological angiogenic stimuli appear not to be additive.
血管灌注产生的切应力引起的内皮细胞（endothelial cell，EC）反应在循环稳态中发挥重要作用，而异常反应与高血压和动脉粥样硬化等血管疾病有关。体外受到高切应力的 EC 会改变其形态、功能和基因表达。目前，切应力信号的机械转导的分子基础和传感机制的身份尚不清楚，许多候选者正在研究中。将这些发现转化为体内仍然具有挑战性。血管内皮生长因子（vascular endothelial growth factor，VEGF）依赖于血流的一氧化氮释放在重塑骨骼肌微循环中的作用已经得到证实，无论是在高剪切应力（活性、扩张）还是低剪切应力（超负荷、缺血）下，尽管它们与血管生成的时间关系不同。很明显，生长因子水平可能只提供一个许可的环境，而受体水平的改变可能是一个可行的治疗靶点。体内的血管生成似乎是一个分级现象，在刺激物撤出时毛细血管的退化可能很快。生理血管生成刺激物的组合似乎不是相加的。
