title: Balance between angiopoietin-1 and angiopoietin-2 is in favor of angiopoietin-2 in atherosclerotic plaques with high microvessel density.
abstract: BACKGROUND
  Atherosclerotic plaque microvessels are associated with plaque hemorrhage and rupture. The mechanisms underlying plaque angiogenesis are largely unknown. Angiopoietin (Ang)-1 and -2 are ligands of the endothelial receptor Tie-2. Ang-1 induces formation of stable vessels, whereas Ang-2 destabilizes the interaction between endothelial cells and their support cells. We studied the expression patterns of Ang-1 and -2 in relation to plaque microvessels.
  
  
  RESULTS
  Carotid endarterectomy specimens were studied (n = 100). Microvessel density (MVD) was correlated with the presence of macrophages and with a (fibro)atheromatous plaque phenotype. A negative correlation was observed between Ang-1 expression and MVD. A positive correlation was observed between the ratio of Ang-2/Ang-1 and MVD. Ang-2 expression was correlated with matrix metalloproteinase-2 (MMP-2) activity. Immunohistochemical staining of Ang-1 was observed in smooth muscle cells, whereas Ang-2 was detected in endothelial cells, smooth muscle cells and macrophages.
  
  
  CONCLUSIONS
  In plaques with high MVD, the local balance between Ang-1 and Ang-2 is in favor of Ang-2. Plaque Ang-2 levels are associated with MMP-2 activity. Ang-2-induced MMP-2 activity might play a role in the development of (unstable) plaque microvessels.
authors.affiliation: University Medical Center, Utrecht, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Post
authors.forename: Wouter
authors.initials: W
authors.lastname: Peeters
authors.forename: Els
authors.initials: E
authors.lastname: Busser
authors.forename: Dennis
authors.initials: D
authors.lastname: Lamers
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D001808:Blood Vessels / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008833:Microcirculation; D013194:Staining and Labeling
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9