Department of Physiology, Amsterdam UMC, Amsterdam Cardiovascular Sciences, Microcirculation, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Int J Mol Sci. 2024 May 31;25(11):6047. doi: 10.3390/ijms25116047.
Endothelial cells (ECs) line the inner surface of all blood vessels and form a barrier that facilitates the controlled transfer of nutrients and oxygen from the circulatory system to surrounding tissues. Exposed to both laminar and turbulent blood flow, ECs are continuously subject to differential mechanical stimulation. It has been well established that the shear stress associated with laminar flow (LF) is atheroprotective, while shear stress in areas with turbulent flow (TF) correlates with EC dysfunction. Moreover, ECs show metabolic adaptions to physiological changes, such as metabolic shifts from quiescence to a proliferative state during angiogenesis. The AMP-activated protein kinase (AMPK) is at the center of these phenomena. AMPK has a central role as a metabolic sensor in several cell types. Moreover, in ECs, AMPK is mechanosensitive, linking mechanosensation with metabolic adaptions. Finally, recent studies indicate that AMPK dysregulation is at the center of cardiovascular disease (CVD) and that pharmacological targeting of AMPK is a promising and novel strategy to treat CVDs such as atherosclerosis or ischemic injury. In this review, we summarize the current knowledge relevant to this topic, with a focus on shear stress-induced AMPK modulation and its consequences for vascular health and disease.
内皮细胞（ECs）排列在所有血管的内表面，形成一个屏障，促进营养物质和氧气从循环系统向周围组织的受控转移。内皮细胞暴露于层流和湍流血流中，持续受到不同的机械刺激。已经证实，与层流（LF）相关的切应力具有抗动脉粥样硬化作用，而具有湍流（TF）的区域的切应力与 EC 功能障碍相关。此外，ECs 表现出对生理变化的代谢适应，例如在血管生成过程中从静止状态到增殖状态的代谢转变。AMP 激活的蛋白激酶（AMPK）是这些现象的核心。AMPK 在几种细胞类型中作为代谢传感器发挥核心作用。此外，在 ECs 中，AMPK 对机械敏感，将机械感觉与代谢适应联系起来。最后，最近的研究表明，AMPK 失调是心血管疾病（CVD）的核心，而 AMPK 的药理学靶向是治疗动脉粥样硬化或缺血性损伤等 CVD 的一种有前途的新策略。在这篇综述中，我们总结了与这一主题相关的最新知识，重点介绍了剪切应力诱导的 AMPK 调节及其对血管健康和疾病的影响。
