Study of the pulmonary vasculaturein chronic lung disease : role of GCN2

Pulmonary hypertension (PH) is a chronic disorder of the pulmonary circulation that often associates with other respiratory diseases such as pulmonary fibrosis (PF). The disappointing results of PH-specific therapies in patients with PF emphasize the need to better understand the underlying pathophysiologic mechanisms. Firstly, we validated an animal model of group III PH-PF that mimics most of the features seen in the human disease, such as lung and arterial remodeling, increased pulmonary pressures and right ventricular dysfunction. Next, we explored the involvement of the GCN2/eIF2α pathway in the development of PH during PF. We showed that GCN2 is dysregulated in both PF patients and in an animal model of combined PF-PH, and that rats deleted for GCN2 display aggravated PF and PH as well as increased vascular permeability, suggesting causative implication of GCN2 dysregulation in PF and/or PH development. Further studies should pave the way for future therapeutic opportunities.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202