Mechanoregulation of Vascular Endothelial Growth Factor Receptor 2 in Angiogenesis.
Mechanoregulation of Vascular Endothelial Growth Factor Receptor 2 in Angiogenesis.
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血管生成中血管内皮生长因子受体 2 的机械调节。
DOI：
10.3389/fcvm.2021.804934
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发表时间：
2021
影响因子：
3.6
通讯作者：
Sewell-Loftin MK
中科院分区：
文献类型：
--
作者：
Miller B;Sewell-Loftin MK
构成体内血管系统的内皮细胞表现出广泛的机械传递行为和对生物力学刺激的反应，这些行为和反应共同控制着整个血管的结构和功能。这种机械敏感活动允许血管在发育过程中根据需要收缩、扩张、生长或重塑，以及正常的生理功能，同样的过程在不同的疾病状态下可能会被失调。机械转导代表细胞对机械力的反应，将这些因素转化为化学或电信号，从而改变各种细胞信号通路的激活。了解生物力学是如何推动健康和疾病组织中的血管生长的，可以创造出新的治疗策略，要么加强要么阻止这些过程，以帮助治疗不同的疾病。在心血管系统中，血管生成是由血管内皮生长因子(VEGFR-2)与血管内皮生长因子受体2(VEGFR-2)结合，促进血管发育。然而，切应力、基质硬度和间质流动等物理力也是血管生成的主要驱动力和效应器，新的研究表明，机械力可能调节VEGFR-2的磷酸化。事实上，VEGFR-2的激活与已知的机械生物学因素有关，包括ERK/MAPK、c-Src、Rho/ROCK和YAP/TAZ。在血管疾病状态下，内皮细胞可能会受到机械刺激的改变，从而影响控制血管生成的途径。正常化和抑制与肿瘤生长相关的血管生成一直是抗癌治疗的策略。在再生医学领域，利用血管生成的生物力学调节可以增强血管形成的策略，以治疗包括缺血在内的各种心血管疾病，或者允许开发新型组织工程支架。本文将重点介绍VEGFR-2在血管内皮细胞(ECs)中的作用及其与其他力学转导途径的相互作用，并讨论VEGFR-2的激活与细胞外基质(ECM)中生物机械力的关系，以帮助治疗血管生长功能障碍的疾病。
The endothelial cells that compose the vascular system in the body display a wide range of mechanotransductive behaviors and responses to biomechanical stimuli, which act in concert to control overall blood vessel structure and function. Such mechanosensitive activities allow blood vessels to constrict, dilate, grow, or remodel as needed during development as well as normal physiological functions, and the same processes can be dysregulated in various disease states. Mechanotransduction represents cellular responses to mechanical forces, translating such factors into chemical or electrical signals which alter the activation of various cell signaling pathways. Understanding how biomechanical forces drive vascular growth in healthy and diseased tissues could create new therapeutic strategies that would either enhance or halt these processes to assist with treatments of different diseases. In the cardiovascular system, new blood vessel formation from preexisting vasculature, in a process known as angiogenesis, is driven by vascular endothelial growth factor (VEGF) binding to VEGF receptor 2 (VEGFR-2) which promotes blood vessel development. However, physical forces such as shear stress, matrix stiffness, and interstitial flow are also major drivers and effectors of angiogenesis, and new research suggests that mechanical forces may regulate VEGFR-2 phosphorylation. In fact, VEGFR-2 activation has been linked to known mechanobiological agents including ERK/MAPK, c-Src, Rho/ROCK, and YAP/TAZ. In vascular disease states, endothelial cells can be subjected to altered mechanical stimuli which affect the pathways that control angiogenesis. Both normalizing and arresting angiogenesis associated with tumor growth have been strategies for anti-cancer treatments. In the field of regenerative medicine, harnessing biomechanical regulation of angiogenesis could enhance vascularization strategies for treating a variety of cardiovascular diseases, including ischemia or permit development of novel tissue engineering scaffolds. This review will focus on the impact of VEGFR-2 mechanosignaling in endothelial cells (ECs) and its interaction with other mechanotransductive pathways, as well as presenting a discussion on the relationship between VEGFR-2 activation and biomechanical forces in the extracellular matrix (ECM) that can help treat diseases with dysfunctional vascular growth.