Szekanecz Z, Shah M R, Harlow L A, Pearce W H, Koch A E
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Pathobiology. 1994;62(3):134-9. doi: 10.1159/000163891.
Angiogenesis, the growth and proliferation of blood vessels, may be important in the pathogenesis of atherosclerosis and thus in human atherosclerotic abdominal aortic aneurysms (AAAs). Endothelial migration or chemotaxis is a vital component of the angiogenic response. Here, human aortic endothelial cells (hAECs) were used to investigate the effect of AAA tissue supernatants on hAEC chemotaxis. AAA tissue conditioned media were found to be chemotactic for hAECs. We have previously shown that the angiogenic cytokines interleukin (IL)-8, and tumor necrosis factor (TNF)-alpha are present in AAAs and normal aortic explant conditioned 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 soluble mediators contributed to the chemotactic activity of these supernatants, conditioned media were preincubated with either neutralizing anti-IL-8, anti-TNF-alpha, anti-bFGF antibodies or control serum. Anti-IL-8 and anti-TNF-alpha significantly inhibited AAA tissue supernatant-induced hAEC chemotaxis (p < 0.05), while anti-bFGF did not (p not significant). These results indicate that IL-8 and TNF-alpha may be important in chemotactic activity for hAECs in vitro and possibly in AAA neovascularization. The abrogation of angiogenesis using neutralizing antibodies may be a future goal in the therapy of certain disease states such as AAA where angiogenesis plays an important role.
血管生成,即血管的生长和增殖,在动脉粥样硬化的发病机制中可能起重要作用,因而在人类动脉粥样硬化性腹主动脉瘤(AAA)中也可能如此。内皮细胞迁移或趋化性是血管生成反应的一个重要组成部分。在此,使用人主动脉内皮细胞(hAECs)来研究AAA组织上清液对hAEC趋化性的影响。发现AAA组织条件培养基对hAECs具有趋化作用。我们之前已经表明,血管生成细胞因子白细胞介素(IL)-8和肿瘤坏死因子(TNF)-α存在于AAA和正常主动脉外植体条件培养基中。目前,我们发现这些上清液中还能检测到碱性成纤维细胞生长因子(bFGF)和血小板衍生生长因子。为了确定这些可溶性介质中的某些是否促成了这些上清液的趋化活性,将条件培养基与中和性抗IL-8、抗TNF-α、抗bFGF抗体或对照血清进行预孵育。抗IL-8和抗TNF-α显著抑制了AAA组织上清液诱导的hAEC趋化性(p<0.05),而抗bFGF则没有(p无显著性差异)。这些结果表明,IL-8和TNF-α可能在体外对hAECs的趋化活性中起重要作用,并且可能在AAA新生血管形成中起作用。使用中和抗体消除血管生成可能是某些疾病状态(如血管生成起重要作用的AAA)治疗的未来目标。