Abstract 14136: Enhanced Angiogenesis in Adventitia Promotes Plaque Formation in Abdominal Aorta of Apolipoprotein E-deficient Mice
Background: Exaggerated formation of vasa vasorum (VV) was detected along with atherosclerotic plaque progression. In advanced lesions, VV invades into plaques and acts as conduits to supply inflammatory cells and lipids into them. It was reported that enhanced angiogenesis in adventitia promoted lesion progression after mechanical vascular injuries. However, it remains unclear whether enhanced VV could promote hyperlipidemia-induced plaque formation.
Methods: Slow releasing form (30 days) of basic fibroblast growth factor (bFGF) was administered focally to augment VV. bFGF (100μg/body) incorporated in acid gelatin hydrogel microspheres (AGHMs) (bFGF+AGHM, n=10), AGHMs alone (AGHM, n=7), PBS(control, n=8) was injected into periaortic areas of retroperitoneal space of 10 to 11-week-old male ApoE-deficient mice. After 13 weeks, the abdominal aortas were harvested with perivascular soft tissues. The adventitial micro-vessels and macrophages were visualized by staining with Lycopersicon Esculentum (Tomato) lectin and anti-Mac3 antibody. Early phase observation was performed at 2, 3 and 4 weeks after the operation (n=3 for each time points). The same procedures were performed in age-matched wild-type mice (n=4 for each groups).
Results: Larger lesions were observed only in bFGF+AGHM group (bFGF+AGHM: 3.4x104 ± 0.7 x104 μm2, AGHM:0.8 x104 ± 0.7x104 μm2, control 0 μm2, p=0.0002) at 13 weeks. Plaque formation was associated with augmented VV. When the aortic section were divided into 16 radial areas, there was a relation between the number of capillaries and the plaque size (r=0.69, p<0.0001). At early phase, proliferation of VV and accumulation of macrophages were observed prior to plaque formation, though invasion of VV into plaques was not observed at time points. In wild-type mice, although bFGF induced VV proliferation, lesion formation was not observed.
Conclusions: Under hyperlipidemic conditions, adventitial administration of bFGF induces VV development, which potentially accelerates plaque formation and progression. Augmented VV might influence plaque progression not only in advanced lesion but also in initial one via inflammatory cell recruitment in adventita.
- © 2010 by American Heart Association, Inc.