Table 1: Biological actions of endogenous inhibitors of angiogenesis.

Endogenous inhibitorFunctions

PEDF, serine proteaseIncreases survival of neuronal cell, preserves the integrity of neuronal cells; protects neuronal cells from apoptosis,
decreases proliferating endothelial cells,
decreases expression of inflammatory molecules like TNF and iNOS.

Angiostatin, cleaved product of plasminogen containing the kringle domains 1–4Increases apoptosis of proliferating vascular endothelial cells,
decreases proliferation and migration of endothelial cells,
decreases recruitment and adhesion of inflammatory cells to the endothelium, and decreases transmigration of inflammatory cells.

Endostatin, fragment of collagen XVIIIIncreases apoptosis and decreases migration of cells involved in active neovascularisation, blocks the binding of VEGF to KDR/Flk-1, and decreases spontaneous release of VEGF from endothelial cell culture,
structurally supports role of the Bruch’s membrane.

TIMP3, inhibitor of matrix metalloproteinaseIncreases apoptosis and decreases migration of cells involved in active neovascularisation, blocks the binding of VEGF to KDR/Flk-1,
structurally supports role of the Bruch’s membrane.

Vasostatin, a derivative from the NH2 terminal domain of a calcium binding protein calreticulinDecreases proliferation of endothelial cells,
decreases adhesion of leukocytes to endothelium,
decreases expression of vascular destabilising factor angiopoietin 2.

Plasminogen kringle 5, cleaved product of plasminogen containing the kringle domain 5Increases proliferation and decreases migration of endothelial cells,
increases apoptosis of endothelial cells,
increases infiltration of inflammatory cells.

Thrombospondin-1, glycoproteinDecreases apoptosis of endothelial cells,
decreases expression of inflammatory molecules.