title: AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells.
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.
  
  
  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.
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Cardiovascular Science of Ministry of Education, Peking University Health Science Center, Beijing, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.forename: Yingying
authors.initials: Y
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.forename: Chenghong
authors.initials: C
authors.lastname: Li
authors.forename: Xuefen
authors.initials: X
authors.lastname: Xie
authors.forename: John Y-J
authors.initials: JY
authors.lastname: Shyy
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000637:transplantation; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology / Q000201:enzymology*; D053686:Fetal Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000637:transplantation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009097:Multienzyme Complexes / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009097:Multienzyme Complexes; D011720:Pyrazoles; D011743:Pyrimidines; D012265:Ribonucleotides; D042461:Vascular Endothelial Growth Factor A; C516138:dorsomorphin; D009569:Nitric Oxide; D000620:Aminoimidazole Carboxamide; D008148:Lovastatin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide; D019331:NG-Nitroarginine Methyl Ester