Histamine synergistically promotes bFGF‐induced angiogenesis by enhancing VEGF production via H1 receptor

Abstract

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.

Pistacia atlanticaResin Has a Dose-Dependent Effect on Angiogenesis and Skin Burn Wound Healing in Rat

“…bFGF is an important inducer of angiogenesis, in in vitro angiogenesis models of endothelial cells. bFGF could induce angiogenesis, and this action was linked to VEGF production through the activation of endothelial nitric oxide synthase in endothelial cells [ 44 ].…”

Computational models applied to metabolomics data hints at the relevance of glutamine metabolism in breast cancer

“…Both histamine and 1,2-propanediol appeared to be related to the angiogenesis functional node. Histamine is known to promote angiogenesis through vascular epithelial growth factor [39]. On the other hand, sulfoquinovosyl acylpropanediol, an 1,2-propanediol derivate, inhibits angiogenesis in murine models with pulmonary carcinoma [40].…”

Computational metabolomics hints at the relevance of glutamine metabolism in breast cancer

“…Both histamine and 1,2-propanediol appeared to be related to the angiogenesis functional node. Histamine is known to promote angiogenesis through vascular epithelial growth factor (Lu et al, 2013). On the other hand, sulfoquinovosyl acylpropanediol, an 1,2-propanediol derivate, inhibits angiogenesis in murine models with pulmonary carcinoma (Ruike et al, 2018).…”