Abstract Number: PB1976
Meeting: ISTH 2020 Congress
Background: The Transient Receptor Potential Channel 4 (TRPV4) of endothelial cells contributes to many important functions including regulation of Ca2+ homeostasis, cell volume, endothelial barrier permeability and smooth muscle tone.
Aims: The aim of this work is to study TRPV4 role in the transition of endothelial cells toward a pro-inflammatory phenotype.
Methods: We characterize effects of pharmacological activation of TRPV4 channels on both arterial and venous endothelial cells and their protection using TRPV4 antagonists.
Results: We show that activation of TRPV4 channels with GSK1016790A, a potent TRPV4 agonist, triggers robust and sustained Ca2+ influx, which is blocked by both TRPV4 antagonists HC-067047 and RN9893. TRPV4 activation triggered actin cytoskeleton and adherent junction (VE-Cadherin) rearrangement in both arterial and venous endothelial cells and lead to rapid decreases of trans-endothelial electrical resistance. In addition to its effect on endothelial barrier integrity, TRPV4 activation selectively increases ICAM-1 surface expression in arterial and venous endothelial cells, due to the stimulation of ICAM-1 gene expression thanks to the NfκB transcription factor. TRPV4 channel activation also induced apoptosis of venous endothelial cells, while TRPV4 antagonists slowed down apoptosis of endothelial cells, even in the absence of TRPV4 activation.
Conclusions: As Altered barrier integrity, increased adhesion molecule expression and apoptosis are hallmarks of the pro-inflammatory state of endothelial cells, our results indicate that that TRPV4 channel and the resulting calcium influx can induce the transition of both venous and arterial endothelial toward a pro-inflammatory phenotype and suggest that pharmacological inhibition of TRPV4 could protect endothelium in pathology involving dysfunctional endothelial inflammation.
To cite this abstract in AMA style:Beddek K, Raffin F, Borgel D, Saller F, Riccobono D, Boittin F-, Bobe R. TRPV4 Channel Activation Induces the Transition of Venous and Arterial Endothelial Cells Toward a Pro-Inflammatory Phenotype [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/trpv4-channel-activation-induces-the-transition-of-venous-and-arterial-endothelial-cells-toward-a-pro-inflammatory-phenotype/. Accessed January 26, 2022.
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