Cited by 212Nitric Oxide and Endothelin EffectsMetabolism, Diabetes, and CancerProtein Kinase Regulation and GTPase Signaling

AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress

Zhang, Yingjia, Lee, Tzong-Shyuan, Kolb, Erik M., Sun, Kai, Lu, Xiao, Sladek, Frances M., Kassab, Ghassan S., Garland, Theodore +1 more·2006·Arteriosclerosis Thrombosis and Vascular Biology

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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Crossref · 10.1161/01.atv.0000221230.08596.98

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35 of 35 references verified0 citation errors · 0 not checkable

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  • Similar general outcome of metformin, AICAR, atheroprotective flow, and statins on endothelial cells can be found through AMPK activation.

    “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]

  • Metformin has been proven as an anti-inflammatory, especially for the inflammation in diabetes and following postsurgical endotoxin.

    “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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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 › 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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