Grant: Project Grant

The aortic valve is one of the four valves present in a human heart that ensure that blood flows only in one direction. A normal aortic valve is composed of three leaflets. A problem during heart development can lead to a valve with only two leaflets, a condition called bicuspid aortic valve (BAV). It is the most common congenital heart defect in adults. It has a prevalence as high as 2% in the general population. It is associated with a significant increase in the risk of obstruction and calcification of the aortic valve, a condition that can lead to severe cardiac disease and death. There is currently no medical treatment for this condition, only surgical treatment is available. BAV is present in as much as 50% of cases of patients requiring surgery for obstruction of the aortic valve. It is therefore a serious medical condition with an important societal and economic burden. BAV can be found in many individuals from the same family, suggesting that is has a strong genetic component. The genetic mechanisms responsible for this condition are however largely unknown, with only a few genes identified so far. This project proposes to integrate genomic data from different sources to identify the mechanisms involved in BAV and obstruction of the aortic valve. We will use blood and heart tissue samples from patients who had cardiac surgery to obtain genomic data in cases of BAV. We will compare this data to individuals with a normally formed but obstructed aortic valve and individuals with a normal aortic valve. We will use recent bioinformatics tools to integrate this large amount of data. We will also make experiments directly on cardiac cells and tissue to confirm the findings. We plan to identify the genetic mechanisms involved in BAV and how they differ from obstruction of normally formed aortic valve. This could lead to the development of new treatments for obstruction of the aortic valve.