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AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress
Open accessAbstract
AMP-activated protein kinase (AMPK) is a stress-activated protein kinase that is regulated by hypoxia and other cellular stresses that result in diminished cellular ATP levels. Here, we investigated whether AMPK signaling in endothelial cells has a role in regulating angiogenesis. Hypoxia induced the activating phosphorylation of AMPK in human umbilical vein endothelial cells (HUVECs), and AMPK activation was required for the maintenance of pro-angiogenic Akt signaling under these conditions. Suppression of AMPK signaling inhibited both HUVEC migration to VEGF and in vitro differentiation into tube-like structures in hypoxic, but not normoxic cultures. Dominant-negative AMPK also inhibited in vivo angiogenesis in Matrigel plugs that were implanted subcutaneously in mice. These data identify AMPK signaling as a new regulator of angiogenesis that is specifically required for endothelial cell migration and differentiation under conditions of hypoxia. As such, endothelial AMPK signaling may be a critical determinant of blood vessel recruitment to tissues that are subjected to ischemic stress.
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“Further evidence also shows that AMPK lies upstream of the phosphatidylinositol-3-kinase-protein kinase B pathway, which also leads to eNOS activation and NO production [162,164,165].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [165]
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“AMPK has been proven to be essential for ischemic angiogenesis; however, the mechanism by which AMPK promotes angiogenesis is poorly elucidated [165].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [165]
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Metadata
- Authors
- Nagata, D., Mogi, M., & Walsh, K.
- Affiliations
- Boston University (US)
- Corresponding author
- Walsh, Kenneth
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 278
- Issue
- 33
- Pages
- 31000-31006
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2070475419
- Cited by
- 331
- References
- 58
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 14 · 2020: 18 · 2019: 12 · 2018: 14 · 2017: 11 · 2016: 8 · 2015: 20 · 2014: 24 · 2013: 14 · 2012: 22
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Heart Foundation
- National Institutes of Health (AG17241, AR40197, AG15052)
- National Institute on Aging (AG17241, AG15052, R01AG017241)
- National Heart, Lung, and Blood Institute (HL-66957, P01HL066957)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-40197, R01AR040197)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- AMPK, AMPK signaling, angiogenesis, hypoxia, endothelial cells, human umbilical vein endothelial cells, Akt signaling, endothelial cell migration, tube formation, vascular endothelial growth factor, ischemia
- MeSH terms
- Hypoxia, Biocompatible Materials, Capillaries, Cell Movement, Cells, Cultured, Collagen, Drug Combinations, Endothelium, Vascular, Humans, Laminin, Multienzyme Complexes, Proteoglycans, Proto-Oncogene Proteins, Stress, Physiological, Umbilical Veins, Signal Transduction, Protein Serine-Threonine Kinases, Neovascularization, Physiologic, Proto-Oncogene Proteins c-akt, AMP-Activated Protein Kinases
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