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Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2644-51. doi: 10.1161/ATVBAHA.112.252544. Epub 2012 Sep 13.

Fibroblast growth factor-2 is required for vasa vasorum plexus stability in hypercholesterolemic mice.

Author information

1
Departments of Surgery, Vascular Section (J.I.M., A.J.-H.P., J.K., T.Z.W., M.J.M.-K.), Immunology and Microbiology (S.K.), Medicine, Cardiology Section (S.L.S.), and Thayer School of Engineering (L.G.Z.), Dartmouth Medical School, Lebanon, NH; and Department of Internal Medicine, Cardiovascular Medicine Section, Yale University School of Medicine, New Haven, CT (M.S.).
#
Contributed equally

Abstract

OBJECTIVE:

Vasa vasorum are angiogenic in advanced stages of human atherosclerosis and hypercholesterolemic mouse models. Fibroblast growth factor-2 (FGF-2) is the predominant angiogenic growth factor in the adventitia and plaque of hypercholesterolemic low-density lipoprotein receptor-deficient/apolipoprotein B(100/100) mice (DKO). FGF-2 seems to play a role in the formation of a distinct vasa vasorum network. This study examined the vasa vasorum structure and its relationship to FGF-2.

METHODS AND RESULTS:

DKO mice treated with saline, antiangiogenic recombinant plasminogen activator inhibitor-1(23) (rPAI-1(23)), or soluble FGF receptor 1 were perfused with fluorescein-labeled Lycopersicon esculentum lectin. Confocal images of FGF-2-probed descending aorta adventitia show that angiogenic vasa vasorum form a plexus-like network in saline-treated DKO similar to the FGF-2 pattern of distribution. Mice treated with rPAI-1(23) and soluble FGF receptor 1 lack a plexus; FGF-2 and vasa vasorum density and area are significantly reduced. A perlecan/FGF-2 complex is critical for plexus stability. Excess plasmin produced in rPAI-1(23)-treated DKO mice degrades perlecan and destabilizes the plexus. Plasmin activity and plaque size measured in DKO and DKO/plasminogen activator inhibitor-1(-)(/-) mice demonstrate that elevated plasmin activity contributes to reduced plaque size.

CONCLUSIONS:

An FGF-2/perlecan complex is required for vasa vasorum plexus stability. Elevated plasmin activity plays a significant inhibitory role in vasa vasorum plexus and plaque development.

PMID:
22982464
PMCID:
PMC3819102
DOI:
10.1161/ATVBAHA.112.252544
[Indexed for MEDLINE]
Free PMC Article

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