
handle: 10616/48852
About 1% of the population is born with an aortic valve composed of only two cusps, called a bicuspid aortic valve. Bicuspid aortic valve is associated with a high risk of both aortic valve disease and ascending aortic dilatation, which develop at a significantly earlier age than in patients with a normal tricuspid aortic valve. No medical therapy exists for either of the conditions and current surgical treatments have substantial limitations. Tissue engineering is a potential future treatment option for valvular heart disease. However, clinical trials have shown that engineered valves exhibit limited durability similarly to conventional biological valves. A possible cause of their failure is an aberrant basement membrane in the scaffolds, but the normal basement membrane in the aortic valve has not been characterized. Moreover, the type and prevalence of valvular disease and aortic dilatation differs between anatomical variants, or phenotypes, of the bicuspid aortic valve, and potential sex differences have not been addressed in this context. Furthermore, the pathological process of ascending aortic dilatation differs between patients with bicuspid and tricuspid aortic valves, which has important implications for pharmacological targets, surveillance, and surgical management. Study I investigated the expression of laminins, a key basement membrane component, in the aortic valve. Valves from deceased donors were studied with immunohistochemistry, which revealed expression of laminin chains ⍺4-5, β1-2, and 𝛾1. A decellularized rat aortic valve scaffold with a retained basement membrane was developed to facilitate studies on the role of basement membrane components in valve regeneration. Study II described sex differences in bicuspid phenotype in relation to valvular and aortic disease in a surgical cohort. Right-left cusp fusion was associated with aortic regurgitation in males, whereas right-non-coronary cusp fusion was associated with regurgitation in females. Furthermore, the 2-sinus phenotype was associated ...
Thesis, 610
Thesis, 610
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