Hypertension artérielle pulmonaire : une approche translationnelle et multidisciplinaire

 

Steeve Provencher

Institut universitaire de cardiologie et de pneumologie de Québec

 

Domaine : santé circulatoire et respiratoire

Programme chercheurs-boursiers cliniciens - Senior

Concours 2015-2016

Pulmonary arterial hypertension (PAH) is characterized by the progressive increase in pulmonary artery pressure and right heart failure. PAH predominantly affects young people between 20-60 years of age. Despite current therapies, most patients exhibit poor exercise capacity and quality of life and die within 5 years. The reasons for this poor prognosis include 1) the insufficient understanding of mechanisms responsible for PAH progression; 2) the lack of good markers identifying patients at an early stage of the disease or predicting future response to therapy; 3) limited understanding of the mechanisms responsible for exercise intolerance and; 4) inappropriate tools to assess the impact of new treatments on patients' well-being.

The proposed research program aims to improve patients' management, quality of life and survival. This will be accomplished along four themes. In Theme 1, I will explore two promising hypotheses that could explain PAH progression, including abnormal development of new vessels (angiogenesis) and deregulation of newly described mechanisms that influence the way genes are expressed (the epigenetic reader BRD4). Importantly, these projects have a high potential to translate research into better patient care since these therapies are already in clinical trial phase for various other diseases. In Theme 2, I will assess the capacity of new blood markers to identify PAH patients and predict their subsequent response to therapy. In Theme 3, I will explore new mechanisms of exercise intolerance in PAH and validate new tools to measure patients' quality of life. These projects are likely to support future drug development. Finally, in Theme 4, I will assess the efficacy of two new therapies in human PAH through a pilot study and a phase 2 clinical trial.

Ultimately, the accomplishment of the current program will open the door to new avenues of investigation and potentially future therapies for this still deadly disease.