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Shear-Stress Activation of AMP-Activated Protein Kinase in Endothelial Homeostasis

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Abstract

As the interface between circulation and the vessel wall, the endothelium dynamically responds to shear-stress imposed by blood flow, which is essential to maintain vascular homeostasis. Results from in vitro studies of cultured vascular endothelial cells and in vivo examination of animal models suggest that adenosine monophosphate-activated protein kinase (AMPK), a master regulator of energy metabolism, is activated by shear stress. Thus, beyond its role in orchestrating cellular energy balance, shear-stress-activated AMPK is crucial for maintaining endothelial homeostasis by its regulation of key molecules such as endothelial nitric oxide synthase (eNOS), Kruppel-like factor 2 (KLF2), and mammalian target of rapamycin (mTOR). Collectively, shear-stress-activated AMPK enhances nitric oxide bioavailability, arrests the cell cycle, and upregulates anti-oxidative and anti-inflammatory genes. These regulations contribute to the atheroprotective effects. This review summarizes some of the recent findings of these mechanotransduction mechanisms, which indicate that AMPK plays an important role in vascular homeostasis in addition to its involvement in energy metabolism.

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Acknowledgment

This work was supported in part by National Institutes of Health grants HL89940 and HL106579 (J.S.).

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  1. Division of Biomedical Sciences, University of California, Riverside, CA, 92521-0121, USA

    John Y.-J. Shyy, Zhen Chen, Wei Wu & Wei Sun

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Shyy, J.YJ., Chen, Z., Wu, W. et al. Shear-Stress Activation of AMP-Activated Protein Kinase in Endothelial Homeostasis. Cel. Mol. Bioeng. 4, 538–546 (2011). https://doi.org/10.1007/s12195-011-0200-0

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