title: Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo.
abstract: Tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) has been implicated in angiogenesis; the growth of new blood vessels from an existing vessel bed. Our aim was to compare pro-angiogenic responses of TRAIL, vascular endothelial growth-factor-A (VEGF-A) and fibroblast growth-factor-2 (FGF-2) either separately (10 ng/mL) or in combination, followed by the assessment of proliferation, migration and tubule formation using human microvascular endothelial-1 (HMEC-1) cells in vitro. Angiogenesis was also measured in vivo using the Matrigel plug assay. TRAIL and FGF-2 significantly augmented HMEC-1 cell proliferation and migration, with combination treatment having an enhanced effect on cell migration only. In contrast, VEGF-A did not stimulate HMEC-1 migration at 10 ng/mL. Tubule formation was induced by all three factors, with TRAIL more effective compared to VEGF-A, but not FGF-2. TRAIL at 400 ng/mL, but not VEGF-A, promoted CD31-positive staining into the Matrigel plug. However, FGF-2 was superior, stimulating cell infiltration and angiogenesis better than TRAIL and VEGF-A in vivo. These findings demonstrate that each growth factor is more effective at different processes of angiogenesis in vitro and in vivo. Understanding how these molecules stimulate different processes relating to angiogenesis may help identify new strategies and treatments aimed at inhibiting or promoting dysregulated angiogenesis in people.
authors.affiliation: Heart Research Institute, Sydney 2042, Australia. sian.cartland@hri.org.au.|Sydney Medical School, University of Sydney, Sydney 2006, Australia. sian.cartland@hri.org.au.
authors.forename: Siân P
authors.initials: SP
authors.lastname: Cartland
authors.affiliation: Heart Research Institute, Sydney 2042, Australia. scott.genner@hri.org.au.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Genner
authors.affiliation: Heart Research Institute, Sydney 2042, Australia. amna.zahoor@alumni.uts.edu.au.
authors.forename: Amna
authors.initials: A
authors.lastname: Zahoor
authors.affiliation: Heart Research Institute, Sydney 2042, Australia. mary.kavurma@hri.org.au.|Sydney Medical School, University of Sydney, Sydney 2006, Australia. mary.kavurma@hri.org.au.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Kavurma
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; D053221:TNF-Related Apoptosis-Inducing Ligand; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen
keywords: FGF-2; Matrigel plug; TRAIL; VEGF-A; angiogenesis; proliferation; scratch assay; tubule formation