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GLP-1 promotes angiogenesis in human endothelial cells in a dose-dependent manner, through the Akt, Src and PKC pathways
Open accessAbstract
Introduction Novel anti-diabetic medications that mimic or augment the physiological actions of GLP-1 improve cardiovascular risk factors in diabetics and GLP-1 has been proposed to have a beneficial role in the cardiovascular system. GLP-1 may have a direct cardioprotective role by decreasing infarct size and protecting from ischemia-reperfusion injury while prolonging survival in rodent models. The mechanisms underlying these observations remain largely unknown. In vitro studies suggest that GLP-1 may promote endothelial cell proliferation, but no study to date has evaluated a potential direct effect of GLP-1 on angiogenesis.Specific aim To evaluate whether GLP-1 affects angiogenesis in humans and to elucidate underlying molecular mechanisms.Material and methods We utilized a 3D culture system where spherules of human umbilical vein endothelial cells (HUVECs) embedded in a collagen scaffold were treated with escalating doses of human recombinant GLP-1 (50-2000 nmol/L) and the formation of new vessels was observed and quantified. Signaling inhibitors were utilized to identify molecular pathways through which GLP-1 promotes angiogenesis.Results We demonstrate that GLP-1 promotes angiogenesis in a dose-dependent manner. The maximum effect on angiogenesis was observed at a GLP-1 dose of 500 nmol/L, while increased angiogenesis occurred in response to doses ranging from 200 nmol/L to 1000 nmol/L. Pre-treatment of the system with Akt inhibitor IV, Bisindolylmaleimide (PKC inhibitor) and src inhibitor I resulted in a significant decrease of the GLP-1 induced angiogenesis.Conclusions This is the first study to demonstrate that GLP-1 promotes angiogenesis in a HUVEC three dimensional in vitro model. This effect requires pharmacological doses and is mediated through the Akt, PKC and src pathways.
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“GLP-1RA-induced angiogenesis appears to be mediated through the PI3K/Akt, PKA, and Src pathways [68].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [68]
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Metadata
- Authors
- Aronis, K. N., Chamberland, J. P., & Mantzoros, C. S.
- Affiliations
- Boston University (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Aronis, Konstantinos N.
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 62
- Issue
- 9
- Pages
- 1279-1286
- ISSN
- 0026-0495 (ISSN-L)
- PMC
- PMC3755020
- OpenAlex
- W1989453119
- Cited by
- 104
- References
- 51
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 11 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 10 · 2017: 13 · 2016: 9 · 2015: 6 · 2014: 8 · 2013: 1
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX000422)
- National Institute on Aging (R01AG032030, AG032030.)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK079929, DK-081913, R01DK058785, R56DK058785, DK079929, DK058785, K24DK081913)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- glucagon-like peptide-1, angiogenesis, human umbilical vein endothelial cells, Akt signaling, Src kinase, protein kinase C, dose-dependent effects, endothelial cell proliferation, cardioprotection, diabetes mellitus
- MeSH terms
- Cells, Cultured, Humans, Protein Kinase C, Neovascularization, Physiologic, src-Family Kinases, Endothelial Cells, Proto-Oncogene Proteins c-akt, Glucagon-Like Peptide 1, Human Umbilical Vein Endothelial Cells
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