Podocan and Wnt Pathway in Left Ventricular Remodeling of Aortic Stenosis

Aortic stenosis is a major cause of morbidity around the world. Progressive aortic stenosis leads to cardiac hypertrophy as a compensatory response. A maladaptive response may lead to heart failure at varying degrees of severity of aortic stenosis in individual patients. The predicting factors for the occurrence of a maladaptive response are not well defined. Therefore current medical therapy for aortic stenosis is considered insufficient and may actually cause harm. The only effective therapy for severe, symptomatic aortic stenosis is aortic valve replacement. It has been found in an experimental study that Podocan determines the degree of cardiac hypertrophy in response to pressure overload via the Wnt-pathway. The possible prognostic role of secreted circulating Wnt modulators in aortic stenosis has also recently gained attention. This project will attempt to establish the prognostic role of circulatory Podocan and Wnt modulators for maladaptive left ventricular response to aortic stenosis. This may help identify patients at particular risk to develop left ventricular dysfunction with aortic stenosis and improve understanding of the mechanisms of left ventricular remodeling in aortic stenosis. Hence, this may also later act as an important background in finding more effective therapies to prevent or delay maladaptive left ventricular response in aortic stenosis.