Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri.
Department of Pharmacology, University of Nevada, Reno, Nevada.
Physiol Rev. 2023 Apr 1;103(2):1247-1421. doi: 10.1152/physrev.00053.2021. Epub 2023 Jan 5.
This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), including their sensing of mechanical stimuli and transduction of mechanical signals that result in the acute functional modulation and longer-term transcriptomic and epigenetic regulation of blood vessels. The mechanosensors discussed include ion channels, plasma membrane-associated structures and receptors, and junction proteins. The mechanosignaling pathways presented include the cytoskeleton, integrins, extracellular matrix, and intracellular signaling molecules. These are followed by discussions on mechanical regulation of transcriptome and epigenetics, relevance of mechanotransduction to health and disease, and interactions between VSMCs and ECs. Throughout this review, we offer suggestions for specific topics that require further understanding. In the closing section on conclusions and perspectives, we summarize what is known and point out the need to treat the vasculature as a system, including not only VSMCs and ECs but also the extracellular matrix and other types of cells such as resident macrophages and pericytes, so that we can fully understand the physiology and pathophysiology of the blood vessel as a whole, thus enhancing the comprehension, diagnosis, treatment, and prevention of vascular diseases.
本文旨在综述血管平滑肌细胞(VSMCs)和内皮细胞(ECs)中的力学转导现状,包括它们对机械刺激的感知以及机械信号的转导,这些信号导致血管的急性功能调节和更长期的转录组和表观遗传调控。讨论的机械感受器包括离子通道、质膜相关结构和受体以及连接蛋白。呈现的机械信号通路包括细胞骨架、整合素、细胞外基质和细胞内信号分子。接下来讨论了转录组和表观遗传学的力学调控、力学转导与健康和疾病的相关性以及 VSMCs 和 ECs 之间的相互作用。在整篇综述中,我们就需要进一步了解的具体主题提出了建议。在结论和展望部分,我们总结了已知内容,并指出需要将血管系统视为一个整体,包括不仅是 VSMCs 和 ECs,还包括细胞外基质和其他类型的细胞,如驻留巨噬细胞和周细胞,以便我们能够全面理解血管作为一个整体的生理学和病理生理学,从而增强对血管疾病的理解、诊断、治疗和预防。