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

First Author  Mollmark JI Year  2012
Journal  Arterioscler Thromb Vasc Biol Volume  32
Issue  11 Pages  2644-51
PubMed ID  22982464 Mgi Jnum  J:207880
Mgi Id  MGI:5559844 Doi  10.1161/ATVBAHA.112.252544
Citation  Mollmark JI, et al. (2012) Fibroblast growth factor-2 is required for vasa vasorum plexus stability in hypercholesterolemic mice. Arterioscler Thromb Vasc Biol 32(11):2644-51
abstractText  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.
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