The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
AMP-Activated Protein Kinase Is Involved in Endothelial NO Synthase Activation in Response to Shear Stress
Abstract
OBJECTIVE: The regulation of AMP-activated protein kinase (AMPK) is implicated in vascular biology because AMPK can phosphorylate endothelial NO synthase (eNOS). In this study, we investigate the regulation of the AMPK-eNOS pathway in vascular endothelial cells (ECs) by shear stress and the activation of aortic AMPK in a mouse model with a high level of voluntary running (High-Runner). METHODS AND RESULTS: By using flow channels with cultured ECs, AMPK Thr172 phosphorylation was increased with changes of flow rate or pulsatility. The activity of LKB1, the upstream kinase of AMPK, and the phosphorylation of eNOS at Ser1179 were concomitant with AMPK activation responding to changes in flow rate or pulsatility. The blockage of AMPK by a dominant-negative mutant of AMPK inhibited shear stress-induced eNOS Ser1179 phosphorylation and NO production. Furthermore, aortic AMPK activity and level of eNOS phosphorylation were significantly elevated in the aortas of High-Runner mice. CONCLUSIONS: Our results suggest that shear stress activates AMPK in ECs, which contributes to elevated eNOS activity and subsequent NO production. Hence, AMPK, in addition to serving as an energy sensor, also plays an important role in regulating vascular tone.
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“As discussed previously, a similar general outcome of metformin, AICAR, atheroprotective flow, and statins on ECs can be found through AMPK activation [245,250,251].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [245]
In the citing paper
“Metformin has been proven as an anti-inflammatory, especially for the inflammation in diabetes and following postsurgical endotoxin [245,246,247].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [245]
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RetractedTSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
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LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
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“AMPK can also directly phosphorylate Ser 1177 in eNOS in an AKT-independent manner, specifically in response to various metabolic stressors [34].”
Wang, Y., Sun, Y., Shen, P., Zhang, W., Pan, W., Zhang, X., Xu, Z., Guan, X., Sun, Y., & Cheng, M. (2026) · Experimental Cell Research · doi:10.1016/j.yexcr.2026.115168
Ferreira, D. C. D. S., Pinto, A. P., Rebelo, M. A., Tanus-Santos, J. E., Tavares, M. E. A., Teixeira, G. R., Carolino, R. D. O. G., Neto, I. V. D. S., de Souza, F. H. V., de Souza, P. E. N., et al. (2026) · Cytokine · doi:10.1016/j.cyto.2026.157223
The AMPK signaling pathway in cell metabolism and human diseases
Zhang, Z., Gu, Y., He, H., Qiao, S., Shao, Y., 龙先铭, Huang, J., Zhang, L., & Zhou, F. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02790-6
Metadata
- Authors
- Zhang, Y., Lee, T.-S., Kolb, E. M., Sun, K., Lu, X., Sladek, F. M., Kassab, G. S., Garland, T., & Shyy, J. Y.-J.
- Affiliations
- University of California, Riverside (US)
- Venue
- Arteriosclerosis Thrombosis and Vascular Biology
- Published
- 2006-06
- Volume
- 26
- Issue
- 6
- Pages
- 1281-1287
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2143950284
- Cited by
- 212
- References
- 35
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 11 · 2021: 15 · 2020: 11 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 8 · 2015: 11 · 2014: 12 · 2013: 17 · 2012: 8
- FWCI
- 9.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-77448, HL55554, R01HL077448)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK053892, R01DK053892)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- AMPK, endothelial nitric oxide synthase, shear stress, endothelial cells, LKB1, nitric oxide production, vascular tone, voluntary running, aorta, pulsatility, flow rate
- MeSH terms
- Animals, Aorta, Cattle, Cells, Cultured, Motor Activity, Multienzyme Complexes, Nitric Oxide, Phosphorylation, Protein Kinases, Pulsatile Flow, Stress, Mechanical, Protein Serine-Threonine Kinases, Endothelial Cells, Mice, Nitric Oxide Synthase Type III, AMP-Activated Protein Kinases
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