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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Cites
1 retracted
Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 480
RetractedTSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
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Davignon, J., & Ganz, P. (2004) · Circulation · doi:10.1161/01.cir.0000131515.03336.f8 · Cited by 2,513
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Hawley, S. A., Boudeau, J., Reid, J. L., Mustard, K. J., Udd, L., Mäkelä, T. P., Alessi, D. R., & Hardie, D. G. (2003) · Journal of Biology · doi:10.1186/1475-4924-2-28 · Cited by 1,694
LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.031 · Cited by 1,650
Flow Effects on Prostacyclin Production by Cultured Human Endothelial Cells
Frangos, J. A., Eskin, S. G., McIntire, L. V., & Ives, C. L. (1985) · Science · doi:10.1126/science.3883488 · Cited by 1,235
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Cited by
Sorted by citations
AMPK and SIRT1: a long-standing partnership?
Ruderman, N. B., Julia Xu, X., Nelson, L., Cacicedo, J. M., Saha, A. K., Lan, F., & Ido, Y. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00745.2009 · Cited by 903
Endothelial fluid shear stress sensing in vascular health and disease
Baeyens, N., Bandyopadhyay, C., Coon, B. G., Yun, S., & Schwartz, M. A. (2016) · Journal of Clinical Investigation · doi:10.1172/jci83083 · Cited by 592
“Some evidence indicates that cells are sensitive to features of pulsatile flow (23, 24), though more systematic studies of these effects are needed.”
BackgroundBalligand, J.-L., Feron, O., & Dessy, C. (2009) · Physiological Reviews · doi:10.1152/physrev.00042.2007 · Cited by 477
“Moreover, the interpretation of the protective effects of AMPK and HIF through the NO-driven modulation of the mitochondrial respiratory chain are further complicated by the recently described AMPK-dependent activation of eNOS (243, 367, 449).”
BackgroundMolecular Biology of Atherosclerosis
Hopkins, P. N. (2013) · Physiological Reviews · doi:10.1152/physrev.00004.2012 · Cited by 469
Molecular mechanisms of the vascular responses to haemodynamic forces
Lehoux, S., Castier, Y., & Tedgui, A. (2006) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01624.x · Cited by 460
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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