Department of Endocrinology and Metabolism, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, 230001, China.
Pharmacol Res. 2020 May;155:104737. doi: 10.1016/j.phrs.2020.104737. Epub 2020 Feb 29.
Endothelial cells (ECs), as one of the most important types of vascular cells, line the innermost layer of all blood vessels throughout human body and regulate vascular tone and homeostasis. ECs are constantly exposed to different types of shear stress (one form of mechanical forces) generated by the flowing blood. Various mechanosensing molecules or complexes existing on EC membrane serve as versatile sensors (termed as mechanosensors) of different patterns and pattern alternation of blood flow. Via these mechanosensors, ECs sense and transduce flow-induced biomechanical signal into different mechano-transduction pathways, leading to altered expression/activity of mechanosensitive transcription factors (TFs), epigenetic modification enzymes, non-coding RNAs, and genes, thereby generating biological responses (i.e., the regulation of endothelial function). Dysfunction of ECs (i.e., endothelial dysfunction) represents one of the most important pathomechanisms for atherosclerosis, hypertension and diabesity. Emerging studies have demonstrated that pharmacological modulators of mechanosensors/TFs/enzymes improve endothelial dysfunction and reduce the incidence of experimental atherosclerosis. Here, I overviewed the important role of endothelial mechanoregulators in vascular endothelium, highlighting the potential of blood flow mimetic compounds to treat endothelial dysfunction and associated atherosclerotic cardiovascular diseases.
内皮细胞（Endothelial cells，ECs）是血管细胞中最重要的类型之一，它们排列在人体所有血管的最内层，调节血管张力和内稳态。ECs 不断暴露于血流产生的各种剪切力（一种机械力形式）中。EC 膜上存在的各种机械感受分子或复合物作为不同血流模式和模式变化的多功能传感器（称为机械传感器）。通过这些机械传感器，ECs 感知并将血流诱导的生物力学信号转导为不同的机械转导途径，导致机械敏感转录因子（Transcription Factors，TFs）、表观遗传修饰酶、非编码 RNA 和基因的表达/活性发生改变，从而产生生物学反应（即内皮功能的调节）。ECs 的功能障碍（即内皮功能障碍）是动脉粥样硬化、高血压和糖尿病等疾病的最重要病理机制之一。新出现的研究表明，机械传感器/TFs/酶的药理学调节剂可改善内皮功能障碍并降低实验性动脉粥样硬化的发生率。在这里，我概述了内皮机械调节剂在血管内皮中的重要作用，强调了血流模拟化合物治疗内皮功能障碍和相关动脉粥样硬化性心血管疾病的潜力。
