Pathobiologie et traitement du rétrécissement aortique calcifié

Patrick Mathieu

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec

 

Domaine : Santé circulatoire et respiratoire

Calcific aortic valve disease (CAVD) is a leading cause of morbidity/mortality. There is no medical treatment for CAVD. Patients with end-stage CAVD must undergo a valve replacement procedure. Bioprostheses (BPs), which are used to replace the native diseased heart valve, are prone to calcification leading to structural failure. Basic mechanism that promote aortic valve calcification (native and BP) is still unresolved, but progresses made in the last several years have shed light on novel processes and may foster the development of new treatments for patients.  The overarching goal of the research program is to investigate molecular mechanisms that drive the development and progression of CAVD.

Owing to funding secured during the last decade the researcher and his team have discovered several novel and important mechanisms that promote the development and progression CAVD.  Specifically, his team was the first to discover the role of autotaxin in the development/progression of CAVD. This work has created considerable interest as autotaxin and or specific receptors could be blocked in order to prevent the progression of CAVD. Also, the researcher and his team identified that enzymes of the ectonucleotidase family promote the deposition of calcium in aortic valve and they are developing novel pharmaceutical compounds as inhibitor of ectonucleotidase. This development may lead to novel treatment. More recently, his lab also discovered that a dysregulation of long non-coding RNA may promote the disease process. In the next several years the applicant and his team will pursue and expand on works performed in the last 10 years.

The translational approach including research in population of patients, isolated cells and pre-clinical animal models developed by the applicant's lab will be an important asset in order to translate the findings to the clinical arena and will foster a highly stimulating environment for trainees and young researchers.