Potential Therapeutic Applications for TRPV4 Antagonists in Lung Disease

Transient receptor potential channel vanilloid 4 (TRPV4) is expressed in numerous cell types in lung, including vascular endothelium and smooth muscle, alveolar macrophages, airway epithelium, and airway smooth muscle. To date, our understanding of the role of TRPV4 in lung disease has been ­largely limited to its involvement in direct acute lung injury and lung injury induced by mechanical stress, specifically ventilator-induced lung injury and that due to high vascular pressure and edema formation in heart failure. We will discuss these areas in some depth. We will also introduce the evidence, albeit limited, for other lung diseases where TRPV4 may potentially play a role, including pulmonary hypertension, airway disease and cough, and thus therapeutics may prove beneficial. Although literature on the translation of bench research related to TRPV4 in lungs to clinical therapeutics is limited, we will discuss the available information.