Recent studies report that transient receptor potential vanilloid 4 (TRPV4) channels are implicated in inflammatory lung diseases including acute lung injury. TRPV4 is a transmembrane Ca2+-permeable cation channel expressed in numerous cell types including vascular endothelial cells (ECs), alveolar epithelial cells, macrophages, and neutrophils. Importantly, TRPV4 activation can induce lung endothelial/epithelial barrier disruption, a critical feature of ischemia-reperfusion injury (IRI), suggesting that TRPV4 antagonism could be of therapeutic value.
Our data demonstrates that TRPV4 activity in ECs is a significant mediator of lung IRI and that inhibition of TRPV4 activity is significantly protective (see Figures below). We also have evidence that TRPV4 activity may be affected by ATP released by pannexin (Panx1) channels on ECs. Thus, our project tests the overall hypothesis that endothelial TRPV4 channel signaling is a critical mediator of lung IRI by inducing endothelial barrier disruption, vascular permeability and leukocyte infiltration.
Our initial study for this project has recently been published: Endothelial Transient Receptor Potential V4 Channels Mediate Lung Ischemia-Reperfusion Injury. Ann Thorac Surg. 113(4):1256-1264, 2022..