Cited by 113Angiogenesis and VEGF in CancerMesenchymal stem cell researchMetabolism, Diabetes, and Cancer

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AMP-Activated Protein Kinase Promotes the Differentiation of Endothelial Progenitor Cells

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Li, Xiaoxia, Han, Yingying, Pang, Wei, Li, Chenghong, Xie, Xuefen, Shyy, John Y.-J., Zhu, Yi·2008·Arteriosclerosis Thrombosis and Vascular Biology

DOI 10.1161/atvbaha.108.172452PMC PMC2737684

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Abstract

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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Authors: Li, X., Han, Y., Pang, W., Li, C., Xie, X., Shyy, J. Y.-J., & Zhu, Y.
Affiliations: University of California, Riverside (US)
ORCID: Li, Xiaoxia
Han, Yingying
Pang, Wei
Li, Chenghong
Zhu, Yi
Venue: Arteriosclerosis Thrombosis and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-10
Volume: 28
Issue: 10
Pages: 1789-1795
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/atvbaha.108.172452
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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AMP-Activated Protein Kinase Promotes the Differentiation of Endothelial Progenitor Cells

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