Les différences liées au sexe dans les mécanismes pathophysiologiques, la présentation, le devenir et le traitement de la sténose aortique calcifiante

 

Marie-Annick Clavel

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

 

Domaine : santé circulatoire et respiratoire

Programme  chercheurs-boursiers - Junior 1

Concours 2017-2018

Aortic valve stenosis (AS) is the narrowing of the valve between the left ventricle and the aorta. This narrowing is an obstacle to the ejection of the blood from the heart. When the disease is severe, the workload of the heart is increased and it may fail. No medical treatment exists to slow down AS progression rate and replacement of the valve by surgery is the only effective treatment.

In AS the mechanisms of development have only been studied in men because they were thought to be similar in men and women. However, we recently demonstrated that there are differences in the valve lesion according to sex. Thus the underlying mechanisms should also be different.

My research program aim to study the differences in AS between men and women. First, we will look at the mechanisms of development of the disease. Second, we will evaluate how the clinical presentation of the disease differs between men and women. Third, we will evaluate the impact of these differences on the management and treatment provided to men and women, as we believe that AS in women is less recognized, and thus under-treated. Fourth, we will test the potential of a medication against a molecule known to be implicated in AS development.

We have a genetically modified mouse model that develops AS with a pattern similar to that of humans. We will compare the development of AS in male and female mice. We will also study a large cohort of patients who have been diagnosed with AS and compare men and women. Finally, we will test the impact of the medication in our mouse model to document the effect of the medication according to sex.

We expect this research will lead toward better diagnosis and treatment of AS in both men and women.