The role of fibroblast growth factor-2 in the vascular effects ofinterleukin-1β in porcine coronary arteries in vivo

Objective: We recently demonstrated that chronic treatment with interleukin-1β (IL-1β), a major inflammatory cytokine found in atherosclerotic lesions, induces coronary arteriosclerotic changes and vasospastic responses to serotonin and histamine in pigs in vivo and that those responses are partially mediated by platelet-derived growth factor (PDGF). This study was designed to examine, first, whether the effects of IL-1β are also partially mediated by fibroblast growth factor-2 (FGF-2), which is another important growth factor in atherosclerotic lesions, and, secondly, whether chronic treatment with FGF-2 per se also induces histological and functional changes in porcine coronary arteries in vivo. Methods: Porcine coronary arteries were aseptically wrapped with cotton mesh absorbing IL-1β with or without neutralizing antibody to FGF-2. In a separate series of experiments porcine coronary arteries were chronically treated with FGF-2 itself in the same manner. Coronary vascular responses in vivo and histological changes were examined 2 weeks after the operation. Results: Coronary vasospastic responses to serotonin and histamine and neointimal formation were induced at the site of the coronary artery where IL-1β was chronically and locally applied. These responses were significantly suppressed by co-treatment with a neutralizing antibody to FGF-2 but not by that with non-immune IgG. Immunostaining revealed the presence of FGF-2 in the endothelial cells, the thickened intima and the media at the IL-1 β-treated site. Furthermore, chronic treatment with FGF-2 also induced coronary vasospastic responses to serotonin and histamine and neointimal formation. Conclusions: These results suggest that the vascular effects of IL-1β may also be mediated by FGF-2 in our swine model and that chronic treatment with FGF-2 also causes coronary arteriosclerotic changes and vasospastic responses in vivo.