Abstract
Introduction and Objectives. Our previous studies showed a role of NGF in pulmonary arterial inflammation, altered reactivity and remodeling. We have here studied NGF expression and role in a new rat model of severe pulmonary hypertension (sPH) combining monocrotaline (MCT) and chronic hypoxia (CH).
Methods. sPH was induced by a single injection of MCT (day (D)1, 60 mg/kg ip) followed by CH (0.5atm, D3 to 28). Anti-NGF blocking antibodies (10µg/kg ip) were administered either preventively at D0-2-9-16-23 or curatively at D15-19-22-26. Pulmonary arterial pressure (Pap) and Fulton index were assessed at D28 for both protocols. Pulmonary arterial NGF secretion was assessed by ELISA. In the preventive protocol, pulmonary arterial inflammation, reactivity and remodelling were also evaluated.
Results. All parameters were significantly increased in sPH rats compared to controls. Treatment with anti-NGF blocking antibodies totally prevented (preventive protocol) and partially reversed (curative protocol) the increased Pap, but did not prevent and only slightly reversed the increased Fulton index. In the preventive protocol, treatment with anti-NGF blocking antibodies partially prevented pulmonary arterial medial thickness, luminal occlusion, presence of concentric and plexiform lesions, as well as pulmonary arterial hyperreactivity and increased secretion of pro-inflammatory cytokines.
Conclusions. We show here that administration of anti-NGF blocking antibodies in vivo in a new rat model of severe PH prevented and reversed, at least partially, increased Pap. Moreover, NGF seems to play a role in various pathophysiological aspects of severe PH, and may therefore be of therapeutical interest in this disease.
- © 2014 ERS