| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2523911 | Biomedicine & Pharmacotherapy | 2016 | 10 Pages |
BackgroundVascular endothelial growth factor (VEGF)-A binds to both VEGF receptor (VEGFR)-1 and VEGFR-2, thereby promoting angiogenesis. It is widely accepted that VEGF-A, especially VEGFR-2, is a central player in angiogenesis, however the role of VEGFR-1 in angiogenesis remains unclear. The present study was conducted to examine the role of VEGFR-1 signaling in angiogenesis, using a quantitative in vivo angiogenesis model.MethodsPolyurethane sponge disks were implanted into dorsal subcutaneous tissue of mice. Angiogenesis was estimated by determining the number of CD31+ vessels by immunohistochemical analysis. The expression of pro-angiogenic factors was quantified by reverse transcription quantitative polymerase chain reaction.ResultsCompared to control IgG-treated mice, the number of CD31+ vessels in the sponge implant was significantly suppressed in anti-VEGF-A neutralizing antibody-treated mice. CD31+ vessel counts were suppressed in VEGFR-1 tyrosine kinase knockout (TKKO) mice, at the same level as in VEGFR-2 tyrosine kinase inhibitor (ZD6474)-treated mice compared to wild-type (WT) mice. The accumulation of VEGFR-1+ cells in granulation tissue was significantly suppressed in VEGFR-1 TKKO mice compared to WT mice. In addition, expression of the pro-angiogenic growth factors, VEGF-A, matrix metalloproteinase-2, interleukin-6, and basic fibroblast growth factor in granulation tissue was suppressed in VEGFR-1 TKKO mice. A bone marrow (BM) transplantation experiment showed that the number of VEGFR-1+ BM-derived cells and angiogenesis were significantly suppressed in VEGFR-1 TKKO mice transplanted with green fluorescent protein (GFP)+ VEGFR-1 TKKO BM compared to WT mice transplanted with GFP+ WT BM.ConclusionsThese results suggest that the VEGFR-1 tyrosine kinase signaling has an effect on angiogenesis. A selective VEGFR-1 agonist/antagonist could be a candidate therapeutic agent to control angiogenesis with recruitment of BM cells.
