Histamine promotes angiogenesis through a histamine H1 receptor-PKC-VEGF-mediated pathway in human endothelial cells

Hatipoglu OF, Nishinaka T, Nishibori M, Watanabe M, Toyomura T, Mori S, Yaykasli KO, Wake H, Takahashi H (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Journal of Pharmacological Sciences Japanese Pharmacological Society

Book Volume: 151

Pages Range: 177-186

Journal Issue: 4

DOI: 10.1016/j.jphs.2023.02.006

Abstract

Histamine is a well-known inflammatory mediator, but how histamine induces angiogenesis remains poorly understood. In the present study, we demonstrated a dose-dependent dynamic tube formation in the human endothelial cell line EA.hy926 in the presence of histamine that was completely blocked by histamine H1 receptor (H1R) and protein kinase C (PKC) inhibitors. However, histamine H2, H3, and H4 receptor inhibitors did not inhibit tube formation, suggesting that H1R–PKC signaling is involved in histamine-induced tube formation. Moreover, we found an H1-specific induction of vascular endothelial growth factor (VEGF) expression. Inhibition of VEGF receptor 2 (VEGFR2) suppressed the histamine-induced tube formation, indicating that VEGF is downstream of histamine signaling. Additionally, we demonstrated that histamine stimulation induces the expression of critical regulators of angiogenesis such as matrix metalloproteinase (MMP)-9 and MMP-14 metalloproteases, as histamine-induced tube formation is blocked by MMP inhibitors. In summary, our study indicates that histamine can activate the H1R in human endothelial cells and thereby promote tube formation through the PKC, MMP, and VEGF signaling pathways.

Authors with CRIS profile

Kürsat Oguz Yaykasli Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Kindai University / 近畿大学 JP Japan (JP) Okayama University / 岡山大学 JP Japan (JP) Shujitsu University / 就実大学 JP Japan (JP)

How to cite

APA:

Hatipoglu, O.F., Nishinaka, T., Nishibori, M., Watanabe, M., Toyomura, T., Mori, S.,... Takahashi, H. (2023). Histamine promotes angiogenesis through a histamine H1 receptor-PKC-VEGF-mediated pathway in human endothelial cells. Journal of Pharmacological Sciences, 151(4), 177-186. https://dx.doi.org/10.1016/j.jphs.2023.02.006

MLA:

Hatipoglu, Omer Faruk, et al. "Histamine promotes angiogenesis through a histamine H1 receptor-PKC-VEGF-mediated pathway in human endothelial cells." Journal of Pharmacological Sciences 151.4 (2023): 177-186.

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