Promoters and Inhibitors of Angiogenesis

Over the past two decades, the identification and study of modes of action of proangiogenic and antiangiogenic factors have yielded an extensive list in both categories (see Table 1). While much of this work has been directed to developing treatments for cancer, considerable progress has also been made in elucidating the importance of these factors in ocular neovascular diseases. This article

Table 1

Proangiogenic and antiangiogenic factors Proangiogenic factors Antiangiogenic factors

Angiogenin

Angioarrestin

Angiopoietin-1

Angiostatin (plasminogen fragment)

Complement factors C3 and C5

Antiangiogenic antithrombin III

Cryptic collagen IV fragment

Cartilage-derived inhibitor (CDI)

Developmentally regulated

CD59 complement

Endothelial locus 1 (Del-1)

Fragment

Ephrins/Ephs

Endostatin (collagen XVIII fragment)

Erythropoietin

Fibronectin fragment

Fibroblast growth factors; acidic

Growth-related

(aFGF) and basic (bFGF)

Oncogene (Gro-p)

Follistatin

Heparinases

Granulocyte colony-stimulating

Heparin hexasaccharide

Factor (G-CSF)

Fragment

Hepatocyte growth factor (HGF)/

Human chorionic

Scatter factor (SF)

Gonadotropin (hCG)

Interleukin-8 (IL-8)

Interferon a/p/g

A5 integrins

Interferon-inducible protein (IP-10)

Leptin

Interleukin-12

Matrix metalloproteinases

Kringle 5 (plasminogen fragment)

Midkine

Metalloproteinase inhibitors (TIMPs)

Notch/D114

2-Methoxyestradiol

Pigment epithelium-derived growth

Pigment epithelium-

Factor

Derived growth factor

Placental growth factor

Placental ribonuclease inhibitor

Platelet-derived endothelial cell

Plasminogen activator

Growth factor (PDECGF)

Inhibitor

Platelet-derived growth factor-B

Platelet factor-4 (PF4)

(PDGF-B)

Pleiotrophin (PTN)

Prolactin 16-kD fragment

Progranulin

Proliferin-related protein (PRP)

Proliferin

Retinoids

Transforming growth factor-a

Slit/Robo4

(TGF-a)

Transforming growth factor-p

Soluble VEGFR1

(TGF-p)

Tumor necrosis factor-a (TNF-a)

Tryptophanyl-tRNA synthase fragment

Vascular endothelial growth factor

VEGFxxxb

(VEGF)

Tetrahydrocortisol-S

Thrombospondin-1

(TSP-1)

Transforming growth factor-p (TGF-p) Vasculostatin Vasostatin (calreticulin fragment)

Table 2


Proangiogenic and antiangiogenic factors


Actions of VEGF in promoting angiogenesis


Reproduced from: Angiogenesis Foundation. Understanding angiogenesis. List of known angiogenic growth factors. Available at: http://www. angio. org/understanding/content_understanding. Html.

Endothelial cell mitogen I Endothelial cell survival factor

Chemoattractant for bone marrow-derived endothelial cells Chemoattractant for monocyte lineage cells I Inducer of synthesis of endothelial nitric oxide synthase and consequent elevation of nitric oxide, itself a promoter of angiogenesis

I Inducer of synthesis of enzymes promoting blood vessel extravasation Matrix metalloproteinases Plasminogen activator

Examines the evidence for those molecules whose roles are best understood in the context of pathological retinal angiogenesis.

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