title: Protective actions of globular and full-length adiponectin on human endothelial cells: novel insights into adiponectin-induced angiogenesis.
abstract: OBJECTIVE
  Adiponectin levels are decreased in diabetes and atherosclerosis. Coexisting hyperglycaemia and systemic inflammation predisposes to dysregulated angiogenesis and vascular disease. We investigated the effect of globular adiponectin (gAd) and full-length adiponectin (fAd) on angiogenesis and pro-angiogenic molecules, i.e. matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF), in human microvascular endothelial cells (HMEC-1).
  
  
  METHODS
  Angiogenesis was assessed by studying capillary tube formation in HMEC-1 on growth factor-reduced Matrigel. Endothelial cell migration assay was performed in a modified Boyden chamber.
  
  
  RESULTS
  Endothelial cell proliferation, in vitro migration and angiogenesis were significantly increased by gAd (mediated by AdipoR1, AMPK-Akt pathways), and gAd significantly increased MMP-2, MMP-9 and VEGF expression levels. The effect of gAd on VEGF appears to be mediated by AdipoR1, whilst the effect of gAd on MMP-2 and MMP-9 appears to be mediated by AdipoR1 and AdipoR2. Only endothelial cell proliferation was significantly increased by fAd in human microvascular endothelial cells and appears to be mediated by AdipoR2. No significant effects on MMP-2, MMP-9 and VEGF were observed. Importantly, gAd decreased glucose and C-reactive protein-induced angiogenesis with a concomitant reduction in MMP-2, MMP-9 and VEGF in HMEC-1 cells.
  
  
  CONCLUSIONS
  We report novel insights into the mechanisms of adiponectin on angiogenesis.
authors.affiliation: Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Raghu
authors.initials: R
authors.lastname: Adya
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D052242:Adiponectin / Q000494:pharmacology; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D010446:Peptide Fragments / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D052242:Adiponectin; D043925:Angiogenesis Inducing Agents; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9