The authors declared they have no conflict of interest.
Histamine synergistically promotes bFGF-induced angiogenesis by enhancing VEGF production via H1 receptor†
Article first published online: 14 MAR 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 5, pages 1009–1019, May 2013
How to Cite
Lu, Q., Wang, C., Pan, R., Gao, X., Wei, Z., Xia, Y. and Dai, Y. (2013), Histamine synergistically promotes bFGF-induced angiogenesis by enhancing VEGF production via H1 receptor. J. Cell. Biochem., 114: 1009–1019. doi: 10.1002/jcb.24440
- Issue published online: 14 MAR 2013
- Article first published online: 14 MAR 2013
- Accepted manuscript online: 5 DEC 2012 08:02AM EST
- Manuscript Accepted: 24 OCT 2012
- Manuscript Received: 16 JUN 2012
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Fundamental Research Funds for the Central Universities. Grant Number: JKY2009001
- Program for Changjiang Scholars and Innovative Research Team in University. Grant Number: PCSIRT-1193
- BASIC FIBROBLAST GROWTH FACTOR;
- SYNERGISTIC ACTION
Histamine, a major mediator present in mast cells that is released into the extracellular milieu upon degranulation, is well known to possess a wide range of biological activities in several classic physiological and pathological processes. However, whether and how it participates in angiogenesis remains obscure. In the present study, we observed its direct and synergistic action with basic fibroblast growth factor (bFGF), an important inducer of angiogenesis, on in vitro angiogenesis models of endothelial cells. Data showed that histamine (0.1, 1, 10 µM) itself was absent of direct effects on the processes of angiogenesis, including the proliferation, migration, and tube formation of endothelial cells. Nevertheless, it could concentration-dependently enhance bFGF-induced angiogenesis as well as production of vascular endothelial growth factor (VEGF) from endothelial cells. The synergistic effect of histamine on VEGF production could be reversed by pretreatments with diphenhydramine (H1-receptor antagonist), SB203580 (selective p38 mitogen-activated protein kinase (MAPK) inhibitor) and L-NAME (nitric oxide synthase (NOS) inhibitor), but not with cimetidine (H2-receptor antagonist) and indomethacin (cyclooxygenase (COX) inhibitor). Moreover, histamine could augment bFGF-incuced phosphorylation and degradation of IκBα, a key factor accounting for the activation and translocation of nuclear factor κB (NF-κB) in endothelial cells. These findings indicated that histamine was able to synergistically augment bFGF-induced angiogenesis, and this action was linked to VEGF production through H1-receptor and the activation of endothelial nitric oxide synthase (eNOS), p38 MAPK, and IκBα in endothelial cells. J. Cell. Biochem. 114: 1009–1019, 2013. © 2012 Wiley Periodicals, Inc.