Abstract 5195: Forced Angiogenesis in Adventitia Promotes Plaque Formation in Abdominal Aorta of Apolipoprotein E-deficient Mice

Abstract

Background: Accumulating evidence suggests that exaggerated formation of vasa vasorum plays an important role in the pathogenesis of atherosclerotic plaque progression. It was reported that enhanced angiogenesis in adventitia promoted lesion progression after mechanical vascular injuries. However, it remains unclear whether augmented angiogenesis in adventitia could promote hyperlipidemia-induced atherosclerotic lesion formation. Methods: We investigated whether local administration of slow-releasing form (30 days) of basic fibroblast growth factor (bFGF) promotes plaque progression with enhanced perivascular angiogenesis. bFGF (100 μ g/body) incorporated in acid gelatin hydrogel microspheres (AGHMs) (bFGF+AGHM group, n=4), AGHMs (AGHM group, n=7), or PBS (control group, n=9) was administrated into periaortic areas of retroperitoneal space of 10 to 11-week-old male ApoE-deficient mice. The mice were fed on western type diet. The abdominal aorta was harvested with perivascular soft tissues at 13 weeks after the operation. Staining with Lycopersicon Esculentum (Tomato) lectin was performed to visualize micro-vessels at 5 different sections from each aorta. Results : Larger lesions were observed only in the bFGF+AGHMs group ( bFGF+AGHM: 3.5×10 4 ±1.2 × 10 4 μ m 2 , AGHM:0.8 × 10 4 ±0.7×10 4 μ m 2 , control 0 μ m 2 , p<0.005). Plaque formation was associated with increased neovascularization in the adventitia. When the aortic section were divided into 16 radial areas, there was a relation between the number of capillaries and the plaque size (r=0.77, p<0.001). In time course study, proliferation of vasa vasorum and accumulation of Mac3-positive macrophages were observed prior to atherosclerotic lesion formation. Conclusions: Local administration of bFGF in adventita induces development of vasa vasorum, which potentially accelerates plaque lesion progression in ApoE-deficient mice.