Abstract:
Cells have an incredible ability to physically interact with neighboring cells and their environment. They can detect and respond to mechanical forces by converting mechanical stimuli into biochemical signals in a process known as mechanotransduction. This is a key process for the adaption of vascular smooth muscle and endothelial cells to altered flow and pressure conditions. Mechanical stimuli, referring to a physical force exerted on cells, are primarily sensed by transmembrane proteins and the actin cytoskeleton, which initiate a cascade of intracellular events, including the activation of signaling pathways, ion channels, and transcriptional regulators. Recent work has highlighted an important role of the transcriptional coactivators YAP/TAZ for mechanotransduction in vascular cells. Interestingly, the activity of YAP/TAZ decreases with age, providing a potential mechanism for the detrimental effects of aging in the vascular wall. In this review, we summarize the current knowledge on the functional role of YAP and TAZ in vascular endothelial and smooth muscle cells for mechanotransduction in homeostasis and disease. In particular, the review is focused on in vivo observations from conditional knockout (KO) models of YAP/TAZ and the potential implications these studies may have for our understanding of vascular disease development.
摘要:
细胞具有令人难以置信的与邻近细胞及其环境物理相互作用的能力。它们可以通过在称为机械传导的过程中将机械刺激转换为生化信号来检测和响应机械力。这是血管平滑肌和内皮细胞适应改变的流量和压力条件的关键过程。机械刺激,指施加在细胞上的物理力,主要由跨膜蛋白和肌动蛋白细胞骨架感知,引发一系列细胞内事件,包括信号通路的激活,离子通道,和转录调节因子。最近的工作强调了转录共激活因子YAP/TAZ在血管细胞中的机械转导中的重要作用。有趣的是,YAP/TAZ的活性随着年龄的增长而降低,为血管壁老化的有害影响提供了潜在的机制。在这次审查中,我们总结了目前有关YAP和TAZ在血管内皮和平滑肌细胞中的机械传导在稳态和疾病中的功能作用的知识。特别是,这篇综述的重点是来自YAP/TAZ条件敲除(KO)模型的体内观察结果,以及这些研究可能对我们理解血管疾病发展的潜在意义.