Abstract
Various angiogenic factors have been shown to play important roles in intraplaque angiogenesis, while little is known about the dynamic expression change and interplay between various angiogenic factors and intraplaque angiogenesis under high cholesterol conditions. New Zealand rabbits underwent balloon injury of the abdominal artery and then were assigned to a control group (n = 15, normal chow) or high cholesterol group (n = 25, 1% high cholesterol diet). At weeks 4, 6, 8, 10, and 12 after acclimation, rabbits (high cholesterol group, n = 5; control group, n = 3) were euthanized. No lesions were observed in the control group. From week 4 to week 12, the expression of vascular endothelial growth factor A (VEGF-A), VEGF receptor 2 (VEGFR-2), fibroblast growth factor 2 (FGF-2), FGF receptor 1 (FGFR-1), platelet-derived growth factor-BB (PDGF-BB), and tumor necrosis factor alpha (TNF-α), the vulnerability index (VI) and the microvessel density (MVD) were significantly elevated in the high cholesterol group; however, PDGF receptor β (PDGFR-β) expression showed little change. Analysis by double-label immunofluorescence (CD31 and Ng2) and FITC-dextran indicated that the neovessels within the plaque were leaky due to a lack of pericytes. As indicated by Pearson's correlation analysis, there was a highly positive correlation between the VI, MVD, macrophage content, and TNF-α level, and the levels of VEGF-A/VEGFR-2 and FGF-2/FGFR-1. However, no correlations were observed between PDGFR-β levels and the VI or MVD. High expression of VEGF-A/VEGFR-2 and FGF-2/FGFR-1 but not of PDGF-BB/PDGFR-β may contribute to immature and inflammatory intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis.