RT Journal Article SR Electronic T1 Role of the TrkA receptor in experimental severe pulmonary hypertension JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP PA4915 DO 10.1183/13993003.congress-2015.PA4915 VO 46 IS suppl 59 A1 Coste, Florence A1 Toussaint, Christian A1 Dubois, Mathilde A1 Courtois, Arnaud A1 Guibert, Christelle A1 Marthan, Roger A1 Savineau, Jean-Pierre A1 Muller, Bernard A1 Michel, Véronique YR 2015 UL https://publications.ersnet.org//content/46/suppl_59/PA4915.abstract AB Introduction. Pulmonary hypertension (PH) is a rare and severe disease, without any curative treatment, that ultimately leads to death. Our previous studies showed a role of the nerve growth factor NGF in severe pulmonary hypertension (SPH) by use of a rat model combining monocrotaline and chronic hypoxia. Using the same model, we have here studied whether the tropomyosin-related kinase A (TrkA) receptor, the NGF high-affinity receptor, is involved in SPH pathophysiology.Methods: SPH was induced in rats by a single injection of MCT (day (D) 1, 60 mg/kg, ip) followed by chronic hypoxia (CH, 0.5 atm, D3 to D28). The TrkA tyrosine-kinase inhibitor K252a was administrated curatively at D15-18-20-25-27 (80 µg/kg, ip). Mean pulmonary arterial pressure (mPAP) and Fulton index were assessed at D28. Pulmonary arterial reactivity, inflammation and remodelling were also evaluated.Results: In SPH rats, all the parameters studied were significantly increased compared to controls. The curative treatment with K252a totally reversed hyperreactivity to PHE, as well as pulmonary artery medial thickening and luminal occlusion. This treatment partially reversed the increase in mPAP (45% inhibition) and Fulton index (40% inhibition) and also partially inhibited increased secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) (27 and 33% inhibition respectively).Conclusions. We show that inhibition of the TrkA receptor in vivo displays curative effects in a rat model of SPH. These results confirm a role of NGF in SPH pathophysiology and demonstrate that targeting of the TrkA receptor may be of therapeutical interest in this disease.