Sasisekharan R, Moses M A, Nugent M A, Cooney C L, Langer R
Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1524-8. doi: 10.1073/pnas.91.4.1524.
Neovascularization is associated with the regulation of tissue development, wound healing, and tumor metastasis. A number of studies have focused on the role of heparin-like molecules in neovascularization; however, little is known about the role of heparin-degrading enzymes in neovascularization. We report here that the heparin-degrading enzymes, heparinases I and III, but not heparinase II, inhibited both neovascularization in vivo and proliferation of capillary endothelial cells mediated by basic fibroblast growth factor in vitro. We suggest that the role of heparinases in inhibition of neovascularization is through depletion of heparan sulfate receptors that are critical for growth factor-mediated endothelial cell proliferation and hence neovascularization. The differences in the effects of the three heparinases on neovascularization could be due to different substrate specificities for the enzymes, influencing the availability of specific heparin fragments that modulate heparin-binding cytokines involved in angiogenesis.
新生血管形成与组织发育、伤口愈合及肿瘤转移的调控相关。许多研究聚焦于类肝素分子在新生血管形成中的作用；然而，关于肝素降解酶在新生血管形成中的作用却知之甚少。我们在此报告，肝素降解酶肝素酶I和III（而非肝素酶II）在体内抑制新生血管形成，在体外抑制碱性成纤维细胞生长因子介导的毛细血管内皮细胞增殖。我们认为，肝素酶在抑制新生血管形成中的作用是通过消耗硫酸乙酰肝素受体实现的，这些受体对于生长因子介导的内皮细胞增殖及新生血管形成至关重要。三种肝素酶对新生血管形成的影响存在差异，可能是由于这些酶具有不同的底物特异性，从而影响了特定肝素片段的可用性，而这些片段可调节参与血管生成的肝素结合细胞因子。
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