Grant: Project Grant

The human heart consists of four chambers that contract in a repeated, rhythmic and synchronized manner to pump blood in the body. The heart also has four valves that ensure that blood flow goes only in one direction. One of these valves is called the aortic valve. The aortic valve lies between the main heart chamber (left ventricle) and the aorta, which is the largest artery that distributes blood to all parts of the body. Calcification of the aortic valve, or more specifically aortic stenosis, is the most frequent heart valve disease and the third leading cause of heart disease in adults. The incidence increases with age, and with the current shift toward an older population, it is becoming a major societal and economic burden. There is currently no medical treatment available other than surgery to replace the diseased native valve by a prosthetic heart valve. It is thus urgent to understand the causes of the disease at the most fundamental levels in order to elucidate new therapeutic options. Many factors are predicted to cause the disease and an important genetic predisposition was demonstrated. However, only a small number of studies have tried to identify the susceptibility genes. In this research program, we plan to expand this work using a series of complementary genomic approaches. This program will take advantage of the large volume of clinical and biological materials that we have collected during the last few years to study patients with aortic stenosis. The most modern genomics and bioinformatics approaches will be used to find new therapeutic targets to treat this condition. Data collected in this proposal will serve for many years and strengthen our research program which ultimately, aims at finding a cure for aortic stenosis. Overall, this proposal will increase our understanding of the disease processes, which will lead to innovative therapeutic strategies to treat this life-threatening and frequent disease.