The bicuspid aortic valve (BAV) is a congenital heart defect which is characterized by the formation of two aortic leaflets instead of the normal three leaflets within the tricuspid aortic valve ... Show moreThe bicuspid aortic valve (BAV) is a congenital heart defect which is characterized by the formation of two aortic leaflets instead of the normal three leaflets within the tricuspid aortic valve (TAV). Whilst all BAV patients have a bicuspid valve, extended patient monitoring has revealed a large variation of disease progression trajectories during a patient’s lifetime. This large variation troubles clinical decision making due to the uncertain proliferation of BAV disease. More knowledge of the biological mechanisms underlying BAV could address that uncertainty and thus help stratify patient risk with more accuracy. Therefore this thesis aims to advance our current understanding regarding the biological impact and developmental mechanisms underlying congenital BAV and BAV related aortopathy. Show less
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... Show moreA 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. Show less
