Elucidating the pathogenesis underlying bicuspid aortic valve disease using new disease models

A bicuspid aortic valve (BAV) is a congenital heart defect in which the heart valve between the left ventricle and the aorta consists of two valve flaps instead of the normal three (tricuspid aortic valve – TAV). In a large proportion of people with a BAV, calcification of the heart valves or a widening of the aorta occurs early in life. It is not yet clear why patients with a BAV are prone to develop valvular calcification and aortic dilatation. The aim of the research described in this thesis is to study the pathogenesis of aortic valve calcification and aortic dilatation in BAV patients with a focus on the role of endothelial cells in these processes. With the research described in this thesis, we have shown that endothelial cells from BAV patients respond differently than cells from people with a TAV. In addition, the endothelial cell activation in the vascular wall of BAV patients is different and dependent on the blood flow. We found two good tissue culture methods to study heart valve calcification and used them to study the role of the protein FHL2 in this process. Dutch Heart Foundation (2013T093)LUMC / Geneeskund