Grant: Project Grant

Mitral Valve Prolapse (MVP) is a common heart valve disorder afflicting 2-3% of the general population. In MVP one or both leaflets are enlarged, which may impact the function of the mitral valve located between the left atrium and the ventricle. One of the main complications of MVP is that it may affect the closing of the mitral valve allowing amounts of blood to flow back into the atrium. Though MVP is frequent we do not know the molecules that promote the development of this condition. Early detection and the identification of actionable targets could lead to the development of new therapies. We have recently discovered that circulating blood proteins were likely involved in the development of MVP. We found that some of these blood proteins promoted a sustained and maladaptive process whereby macrophages, a type of white blood cells, triggered the abnormal synthesis of proteins within the mitral valve leaflets. These findings highlighted for the first time that circulating molecules, blood cells and the mitral valve interact together in promoting the development of MVP. The goal of our CIHR Project grant is to investigate how genes expressed in the blood and mitral valve are modified during MVP. We will use a technique called Mendelian randomization to determine which genes play a determinant role in the development of MVP. Mendelian randomization is often referred to as "Mother Nature's experiment", as it uses inherited gene variants to infer causal relationships between an exposure (e.g. expression of genes) and a disease. We will use Mendelian randomization to identify genes, which could be actionable for the development of future therapies. These molecules will be evaluated on cells from the mitral valve. We will also identify novel markers of MVP by implementing computing algorithms. The findings from this study could be a game changer and help develop novel strategies to treat MVP.