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机械敏感性通道/受体在动脉粥样硬化中的作用。

Role of mechanosensitive channels/receptors in atherosclerosis.

机构信息

Department of Nutrition and Food Science, University of Maryland, College Park, Maryland.

Winston Churchill School, Potomac, Maryland.

出版信息

Am J Physiol Cell Physiol. 2022 May 1;322(5):C927-C938. doi: 10.1152/ajpcell.00396.2021. Epub 2022 Mar 30.

Abstract

Mechanical forces are critical physical cues that can affect numerous cellular processes regulating the development, tissue maintenance, and functionality of cells. The contribution of mechanical forces is especially crucial in the vascular system where it is required for embryogenesis and for maintenance of physiological function in vascular cells including aortic endothelial cells, resident macrophages, and smooth muscle cells. Emerging evidence has also identified a role of these mechanical cues in pathological conditions of the vascular system such as atherosclerosis and associated diseases like hypertension. Of the different mechanotransducers, mechanosensitive ion channels/receptors are gaining prominence due to their involvement in numerous physiological and pathological conditions. However, only a handful of potential mechanosensory ion channels/receptors have been shown to be involved in atherosclerosis, and their precise role in disease development and progression remains poorly understood. Here, we provide a comprehensive account of recent studies investigating the role of mechanosensitive ion channels/receptors in atherosclerosis. We discuss the different groups of mechanosensitive proteins and their specific roles in inflammation, endothelial dysfunction, macrophage foam cell formation, and lesion development, which are crucial for the development and progression of atherosclerosis. Results of the studies discussed here will help in developing an understanding of the current state of mechanobiology in vascular diseases, specifically in atherosclerosis, which may be important for the development of innovative and targeted therapeutics for this disease.

摘要

机械力是影响调节细胞发育、组织维持和功能的众多细胞过程的关键物理线索。机械力的贡献在血管系统中尤为重要,它是胚胎发生所必需的,也是维持包括主动脉内皮细胞、驻留巨噬细胞和血管平滑肌细胞在内的血管细胞的生理功能所必需的。新出现的证据还表明,这些机械线索在血管系统的病理状况中发挥作用,如动脉粥样硬化以及与之相关的疾病,如高血压。在不同的机械转导子中,机械敏感离子通道/受体由于它们参与了许多生理和病理状况而受到关注。然而,只有少数潜在的机械感觉离子通道/受体被证明与动脉粥样硬化有关,它们在疾病发展和进展中的精确作用仍知之甚少。在这里,我们全面介绍了最近研究机械敏感离子通道/受体在动脉粥样硬化中的作用的研究。我们讨论了机械敏感蛋白的不同组及其在炎症、内皮功能障碍、巨噬细胞泡沫细胞形成和病变发展中的特定作用,这些作用对于动脉粥样硬化的发展和进展至关重要。这里讨论的研究结果将有助于了解血管疾病,特别是动脉粥样硬化中机械生物学的现状,这对于这种疾病的创新和靶向治疗的发展可能很重要。

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