The novel role of T2R14 antagonism, by LW129, on VEGF-induced lung endothelial neovascularisation processes in vitro.
- 1Biomedical and Health Innovation Research Centre, Anglia Ruskin University, Cambridge, UK.
- 2Vascular Research Lab, Providence Veterans Affairs Medical Center, Brown University, Providence, Rhode Island, USA.
Abstract
Pulmonary vascular remodelling, driven by dysregulated angiogenesis, is a hallmark of several cardiopulmonary diseases, yet the molecular pathways regulating endothelial responses remain incompletely understood. Bitter taste receptors (T2Rs), traditionally recognised as chemosensory receptors, have emerged as important modulators of vascular function. However, the contribution of T2Rs to pulmonary angiogenesis remains unexplored. Here, we investigated the role of T2R14 in vascular endothelial growth factor (VEGF)-mediated angiogenic responses in human pulmonary microvascular endothelial cells (HPMECs). Using the selective T2R14 antagonist LW129, we examined the effects of T2R14 inhibition on key endothelial angiogenic processes, including VEGF-induced proliferation, migration and capillary-like tube formation in vitro. Pharmacological antagonism of T2R14 significantly attenuated VEGF-driven endothelial proliferative, migratory and morphogenic responses, revealing a novel contribution of T2R14 signalling to pulmonary microvascular angiogenesis. Proteome Profiler analysis identified a range of molecular regulators of angiogenic processes which were dysregulated by LW129 and VEGF exposure, suggesting a potential role for CXCL16, endoglin, FGF-7, and VEGF-C. These findings identify T2R14 as a novel regulator of VEGF-dependent endothelial activation and suggest that targeting T2R14 signalling may represent a therapeutic strategy to limit pathological pulmonary vascular remodelling associated with aberrant angiogenesis.
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BibTeX
@article{spurrierbest2026novel,
title = {{The novel role of T2R14 antagonism, by LW129, on VEGF-induced lung endothelial neovascularisation processes in vitro.}},
author = {Lewis Spurrier-Best and Ellizabeth O Harrington and Havovi Chichger},
journal = {Physiological reports},
year = {2026},
month = oct,
doi = {10.14814/phy2.71168},
url = {https://europepmc.org/article/MED/42960457},
note = {CC BY},
}
RIS
TY - JOUR
TI - The novel role of T2R14 antagonism, by LW129, on VEGF-induced lung endothelial neovascularisation processes in vitro.
AU - Lewis Spurrier-Best
AU - Ellizabeth O Harrington
AU - Havovi Chichger
PY - 2026
DA - 2026/10/30
JO - Physiological reports
DO - 10.14814/phy2.71168
UR - https://europepmc.org/article/MED/42960457
AB - Pulmonary vascular remodelling, driven by dysregulated angiogenesis, is a hallmark of several cardiopulmonary diseases, yet the molecular pathways regulating endothelial responses remain incompletely understood. Bitter taste receptors (T2Rs), traditionally recognised as chemosensory receptors, have emerged as important modulators of vascular function. However, the contribution of T2Rs to pulmonary angiogenesis remains unexplored. Here, we investigated the role of T2R14 in vascular endothelial growth factor (VEGF)-mediated angiogenic responses in human pulmonary microvascular endothelial cells (HPMECs). Using the selective T2R14 antagonist LW129, we examined the effects of T2R14 inhibition on key endothelial angiogenic processes, including VEGF-induced proliferation, migration and capillary-like tube formation in vitro. Pharmacological antagonism of T2R14 significantly attenuated VEGF-driven endothelial proliferative, migratory and morphogenic responses, revealing a novel contribution of T2R14 signalling to pulmonary microvascular angiogenesis. Proteome Profiler analysis identified a range of molecular regulators of angiogenic processes which were dysregulated by LW129 and VEGF exposure, suggesting a potential role for CXCL16, endoglin, FGF-7, and VEGF-C. These findings identify T2R14 as a novel regulator of VEGF-dependent endothelial activation and suggest that targeting T2R14 signalling may represent a therapeutic strategy to limit pathological pulmonary vascular remodelling associated with aberrant angiogenesis.
SN - 2051-817X
ER -