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Int. J. Mol. Sci. 2016, 17(12), 2025; doi:10.3390/ijms17122025

Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo

Heart Research Institute, Sydney 2042, Australia
Sydney Medical School, University of Sydney, Sydney 2006, Australia
Author to whom correspondence should be addressed.
Academic Editor: Shaker A. Mousa
Received: 20 September 2016 / Revised: 24 November 2016 / Accepted: 25 November 2016 / Published: 2 December 2016
(This article belongs to the Special Issue Vascular Biology and Therapeutics)
View Full-Text   |   Download PDF [1748 KB, uploaded 2 December 2016]   |  


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. View Full-Text
Keywords: angiogenesis; proliferation; scratch assay; tubule formation; Matrigel plug; TRAIL; VEGF-A; FGF-2 angiogenesis; proliferation; scratch assay; tubule formation; Matrigel plug; TRAIL; VEGF-A; FGF-2

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Cartland, S.P.; Genner, S.W.; Zahoor, A.; Kavurma, M.M. Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo. Int. J. Mol. Sci. 2016, 17, 2025.

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