Balance between angiopoietin-1 and angiopoietin-2 is in favor of angiopoietin-2 in atherosclerotic plaques with high microvessel density.
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.
Post
Simone
S
University Medical Center, Utrecht, The Netherlands.
Peeters
Wouter
W
Busser
Els
E
Lamers
Dennis
D
Sluijter
Joost P G
JP
Goumans
Marie-José
MJ
de Weger
Roel A
RA
Moll
Frans L
FL
Doevendans
Pieter A
PA
Pasterkamp
Gerard
G
Vink
Aryan
A
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
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9