Main features of nonclassic proangiogenic and antiangiogenic factors
| Factor | Receptors | Signaling Pathwaysa | Angiogenic Activityb | Tumor Growth and Vascularization | Interaction with Other Factorsc | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| In Vitro Assays (ECs) | In Vivo Assay (New Vessel Formation) | |||||||||||
| Differentiation | Proliferation | Migration | Differentiation (Capillary Tube Formation) | CAM | Rabbit Cornea | Sponge Model (Matrigel Plug) | Experimental Ischemia | |||||
| EPO | EPO-RA, EPO-RB | + PI3K/Akt + JAK/STAT | S | S | S | S | = | = | S | S | ↑ ET-1 | |
| ANG-II | AT1-R, AT2-R | + NOS/NO ? | =S | SI | S= | S= | S I | SI | SI | S [I], [S]d | S (?)= | ↑ VEGF |
| ET | ETA-R, ETB-R | + BKca + PGE2/COX | I | S | S | S | S | = | S | = | S | ↑ VEGF |
| AM | AM1-R, AM2-R | + AC + Akt + MAPK | I | S [N] | S | S | S | = | = | S | S | ↑ VEGF (?) |
| PAMP | ? | ? | = | = | = | S | = | = | S | = | S | ↑ VEGF/FGF-2/↑ PDGF (?) |
| Urotensin-II | UT-R | ? | = | N | = | S | S | = | = | = | S(?) | ? |
| Leptin | Ob-Ra, Ob-Rb | + MAPK + STAT-3 | = | S | = | = | S | S | = | = | = | ↑ angiopoietin-2↑ VEGF (?) |
| Adiponectin | AdipoR1, AdipoR2 | + AMP kinase | I | [I] | [I] | = | [I] | S[I] | S | S | S(?) | ↑ FGF-2 (?) |
| Resistin | ? | + PI3K + MAPK | = | S | S | = | = | = | = | = | ↑ VEGF | |
| NPY | Y1-R/Y2-R (Y5-R) | + MAPK | = | S | S | S | = | = | S | S | ? | |
| VIP (PACAP) | VPAC1-R | + PKA + PI3K + MAPK | = | = | = | = | = | = | S | = | = | ↑ VEGF |
| Substance-P | NK1-R | + PLC/PKC + NOS/NO | = | S | S | = | = | S | S | = | = | ? |
| Somatostatin | sst-2R, sst-3R (sst-1R/sst-5R) | - MAPK - NOS/NO | = | I | = | = | = | = | = | = | I | ↓ VEGF |
| Ghrelin | GHS-R1a | - MAPK - PI3K/Akt | S | I | = | I | I | = | = | = | = | ? |
| Natriuretic peptides | A-R/C-R (B-R) | - MAPK - JNK | = | I | I | I | = | = | = | = | = | ↓ VEGF |
BKca, Ca2+-activated large conductance potassium channel; COX, cyclooxygenase; AC, adenylate cyclase; JNK, cJun N-terminal kinase
↵ a >+, stimulation; -, inhibition
↵ b I, inhibition; N, no effect; S, stimulation; =, no findings available
↵ c ↑, up-regulation; ↓, down-regulation
↵ d Brackets indicate unorthodox findings