Table 2

Endogenous angiogenesis inhibitors

Inhibitor

Molecular and physiologic properties


Proteolytic fragments

Angiostatin

38-kD internal fragment of plasminogen (kringles 1-4); kringles 1-3 and kringle 5 also active.

Arrestin

26-kD carboxy-terminal noncollagenous domain of a1 chain of Type IV collagen; inhibits endothelial cell (EC) proliferation.

Antithrombin (cleaved)

53-55-kD cleaved conformation inhibits EC proliferation and tumor growth in mice.

Canstatin

24-kD carboxy-terminal noncollagenous domain of a2 chain of Type IV collagen; inhibits EC proliferation and apoptosis.

Endostatin

20-kD fragment of carboxy-terminal noncollagenous domain of Type XVIII collagen; mechanism of action unknown.

Fibronectin fragments

29-kD amino-terminal and 40-kD carboxy-terminal heparin-binding fragments inhibit EC proliferation.

PEX

Carboxy-terminal hemopexin-like domain of matrix metalloproteinase-2 inhibits EC proliferation and tumor growth in mice.

Prolactin (16-kD)

Naturally occurring 16-kD cleaved amino-terminal fragment of prolactin; retains activity as partial prolactin agonist.

Prothrombin kringle-2

22-kD prothrombin fragment initially isolated from lipopolysaccharide-treated serum.

Restin

22-kD fragment of carboxy-terminal noncollagenous domain of Type XV collagen; 60% homology to murine endostatin.

Vasostatin

Amino-terminal fragment of calreticulin; inhibits EC proliferation and tumor growth in mice.

Interleukins

IL-1

17-kD β-isoform inhibits FGF-stimulated angiogenesis by an autocrine pathway.

IL-4

13-kD lymphokine; inhibits basic FGF-induced angiogenesis.

IL-10

Inhibits tumor vascularity and growth, possibly by decreasing macrophage-derived angiogenic factors.

IL-12

75-kD glycoprotein; inhibits in vivo angiogenesis via IFN-γ - and IP-10-related mechanism.

IL-18

IFN-γ-inducing cytokine; inhibits FGF-stimulated EC proliferation and in vivo angiogenesis.

Interferons

IFN-α

8 to 20-kD glycoproteins secreted by lymphocytes and phagocytes; inhibits EC proliferation and migration.

IFN-β

23-kD glycoprotein derived from fibroblasts and epithelial cells.

IFN-γ

20 to 25-kD glycoprotein secreted by T cells and natural killer cells; cytotoxic to proliferating ECs.

TIMP metallopeptidase inhibitors

TIMP-1 (TIMP metallo-peptidase inhibitor 1)

Soluble 8.5-kD collagenase inhibitor.

TIMP-2

Soluble 21-kD collagenase inhibitor.

TIMP-3

Extracellular matrix-associated collagenase inhibitor.

Other molecules

1,25-(OH)2-vitamin D3

Antiangiogenic effect similar to that of retinoic acid; nonhydroxylated vitamin D3 not active.

2-methoxyestradiol

0.3-kD estrogen metabolite; inhibits EC migration and urokinase plasminogen activator.

Angiopoietin-2

Inhibits angiopoietin-1-mediated activation of EC tyrosine kinase receptor, Tie2; role in vascular remodeling.

EMAP-II

Tumor-derived 20-kD (34 kD proform) inflammatory cytokine.

Gro-β

8-kD CXC chemokine; inhibits tumor growth in mice.

IP-10

8.6-kD CXC chemokine induced by IFNγ -.

Maspin

42-kD serine protease inhibitor (serpin); inhibits EC migration and tumor growth and vascularity in mice.

METH-1, METH-2

110- and 98-kD proteins with metalloprotease and disintegrin-like domains, and carboxy-terminal type 1 TSP-1 repeats.

MIG

11.7-kD CXC chemokine induced by IFN-γ.

p16

Tumor supressor gene; wild type downregulates VEGF expression and inhibits angiogenesis in gliomas.

p53

Tumor suppressor gene; wild type increases TSP-1 expression, decreases VEGF expression.

PEDF

50-kD inhibitor expressed by retinal pigment epithelial cells.

Platelet factor-4

28-kD heparin-binding platelet-derived inhibitory factor.

Proliferin-related protein

Inhibitor of placental angiogenesis in late gestation.

Prostate-specific antigen

Serine protease associated with prostate carcinoma and other tumors.

Protamine

43-kD heparin-binding protein produced by sperm; role in vessel remodeling.

Retinoic acid

0.3-kD inhibitor of EC migration; appears to act as transcriptional regulator.

Soluble FGF receptor

60 to 85-kD circulating binding proteins that may regulate pro-angiogenic activity of FGF.

Transforming growth factor β1

25-kD inhibitor of EC growth and proteolytic activity.

Troponin I

Subunit of troponin complex recently found to be present in cartilage and to inhibit angiogenesis.

TSP-1, TSP-2

450-kD platelet- and fibroblast-derived trimeric glycoproteins.


Burton and Libutti Journal of Biology 2009 8:85   doi:10.1186/jbiol189