Antiangiogenic Factors

Angiogenesis is under tight negative control and factors are expressed that limit neovascularization in a wound healing or hypoxic response. First, oxygenation status is a powerful determinant. Hyperoxia is a potent inhibitor of EC proliferation, angiogenesis, and the expression of key growth factors including VEGF. Inhibitors of angiogenesis include angiostatin, endostatin, interferon-a/p/g, inter-leukins, platelet factor 4, thrombospondin-1, TIMP, and TNF-a. Some MMPs also act as inhibitors. MMP-1 and MMP-3 interfere with integrin binding and MMP-7 and -9 generate angiostatin from plasminogen, thereby inhibiting EC proliferation. Apoptosis of ECs appears to be a key event that mediates the cessation of angiogenesis.

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