AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells
Open accessAbstract
OBJECTIVE: Endothelial progenitor cells (EPCs) can differentiate into endothelial cells (ECs) and participate in postnatal vasculogenesis, but the mechanism of EPC differentiation remains largely unknown. We investigated the role of AMP-activated protein kinase (AMPK) in EPC differentiation and functions. METHODS AND RESULTS: Vascular endothelial growth factor caused the phosphorylation of AMPK, acetyl-coenzymeA (CoA) carboxylase (ACC), and eNOS in human cord blood-derived EPCs. The expression of EC markers, including VE-cadherin and intercellular adhesion molecule1 (ICAM-1), was also increased but blocked by Compound C, an AMPK inhibitor. AICAR, an AMPK agonist, increased the phosphorylation of ACC and eNOS and the expression of EC markers in a time- and dose-dependent manner, which reinforces the positive effect of AMPK on EPC differentiation. The effects of AICAR could be blocked by treatment with L-NAME, an eNOS inhibitor. Functionally, AICAR increased but Compound C decreased the angiogenesis of EPCs in vitro and in vivo. Furthermore, lovastatin promoted the activation of AMPK and eNOS, the expression of EC markers, tube formation, adhesion, and in vivo vasculogenesis of EPCs, which could be blocked by treatment with Compound C. CONCLUSIONS: The activation of eNOS by AMPK during EPC differentiation provides a novel mechanism for the pleiotropic effects of statins in benefiting the cardiovascular system.
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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 [251]
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- Authors
- Li, X., Han, Y., Pang, W., Li, C., Xie, X., Shyy, J. Y.-J., & Zhu, Y.
- Affiliations
- University of California, Riverside (US)
- Venue
- Arteriosclerosis Thrombosis and Vascular Biology
- Published
- 2008-10
- Volume
- 28
- Issue
- 10
- Pages
- 1789-1795
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC2737684
- OpenAlex
- W2121972161
- Cited by
- 113
- References
- 39
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 8 · 2019: 3 · 2018: 9 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 9 · 2013: 8 · 2012: 20
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-77448, R01HL089940, R01HL077448)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- AMPK, endothelial progenitor cells, endothelial differentiation, endothelial nitric oxide synthase, acetyl-CoA carboxylase, AICAR, compound C, lovastatin, statins, angiogenesis, vasculogenesis, vascular endothelial growth factor, VE-cadherin, ICAM-1, L-NAME, tube formation
- MeSH terms
- Acetyl-CoA Carboxylase, Aminoimidazole Carboxamide, Animals, Cell Differentiation, Cells, Cultured, Enzyme Inhibitors, Fetal Blood, Humans, Lovastatin, Mice, Nude, Multienzyme Complexes, Nitric Oxide, Phosphorylation, Pyrazoles, Pyrimidines, Ribonucleotides, Signal Transduction, Biomarkers, Protein Serine-Threonine Kinases, Neovascularization, Physiologic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, NG-Nitroarginine Methyl Ester, Enzyme Activators, Cord Blood Stem Cell Transplantation, Vascular Endothelial Growth Factor A, Endothelial Cells, Mice, Nitric Oxide Synthase Type III, Fetal Stem Cells, AMP-Activated Protein Kinases
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