Hypertension pulmonaire: une approche translationelle et transdiciplinaire

 

Steeve Provencher

Institut universitaire de cardiologie et de pneumologie de Québec

 

Domaine : santé circulatoire et respiratoire

Programme chercheurs-boursiers - Senior

Concours 2016-2017

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) limited understanding of the mechanisms responsible for exercise intolerance in PAH; 3) inappropriate tools to assess the impact of new treatments on patients' well-being and; 4) the lack of confirmation that combination therapy is more effective than mono therapy.

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 progression of pulmonary artery remodelling (narrowing) and stiffness (calcification) in PAH, including the transcription protein RUNX2 and HDAC6, an enzyme modulating the action of important genes in PAH. 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 explore new mechanisms of exercise intolerance in PAH. In theme 3, I will validate new tools to measure patients' quality of life. I will also systematically assess (meta-analysis) the recent clinical trials to get a better estimate of the effects of combination therapy on outcomes that are relevant for PAH patients. Finally, in Theme 4, I will assess the efficacy of a new therapy in human PAH through a pilot study.

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.