INTERLEUKIN-8 AND TUMOR-NECROSIS-FACTOR-ALPHA ARE INVOLVED IN HUMAN AORTIC ENDOTHELIAL-CELL MIGRATION - THE POSSIBLE ROLE OF THESE CYTOKINES IN HUMAN AORTIC ANEURYSMAL BLOOD-VESSEL GROWTH

Angiogenesis, the growth and proliferation of blood vessels, may be im portant in the pathogenesis of atherosclerosis and thus in human ather osclerotic abdominal aortic aneurysms (AAAs). Endothelial migration or chemotaxis is a vital component of the angiogenic response. Here, hum an aortic endothelial cells (hAECs) were used to investigate the effec t of AAA tissue supernatants on hAEC chemotaxis. AAA tissue conditione d media were found to be chemotactic for hAECs. We have previously sho wn that the angiogenic cytokines interleukin (IL)-8, and tumor necrosi s factor (TNF)-alpha are present in AAAs and normal aortic explant con ditioned media. Currently, we have found that basic fibroblast growth factor (bFGF) and platelet-derived growth factor can also be detected in these supernatants. In order to identify whether some of these solu ble mediators contributed to the chemotactic activity of these superna tants, conditioned media were preincubated with either neutralizing an ti-IL-8, anti-TNF-alpha, anti-bFGF antibodies or control serum. Anti-I L-8 and anti-TNF-alpha significantly inhibited AAA tissue supernatant- induced hAEC chemotaxis (p < 0.05), while anti-bFGF did not (p not sig nificant). These results indicate that IL-8 and TNF-alpha may be impor tant in chemotactic activity for hAECs in vitro and possibly in AAA ne ovascularization. The abrogation of angiogenesis using neutralizing an tibodies may be a future goal in the therapy of certain disease states such as AAA where angiogenesis plays an important role.