Abstract

Objective: Patients with a bicuspid aortic valve (BAV) and Marfan syndrome (MFS) have increased susceptibility for development of aortopathy. In the heart, epicardial cells expressing Wilms tumor suppressor protein (Wt1) are known to become activated after myocardial infarction. We hypothesize that epicardium covering the aorta might show a similar response in BAV and MFS in pathologic conditions. Methods: Non- and dilated ascending aorta specimen of BAV (n = 36), tricuspid aortic valve (TAV) (n = 23), and MFS (8) were investigated. The aorta was studied by immunohistochemistry and immunofluorescence, using Wt1 and endothelial nitric oxide, which regulates Wt1 expression. Functionality and therefore activity of Wt1 was confirmed by co-expression with retinaldehyde dehydrogenase-II enzyme in the same cells. Results: The endothelium did not show a difference in the expression of the markers between the groups. In the aortic media Wt1 and eNOS expression were significantly higher in the TAVs as compared to the BAVs and MFS. All groups exhibited Wt1 positive cells in a quiescent stage in the epicardial cells, whereas only the dilated TAVs showed a significant higher Wt1 expression (p < 0.05) in the activated cuboid epicardial cells. Conclusion: In all non-dilated patients, a baseline expression of Wt1 is present in epicardial and vascular smooth muscle cells. A significant increase in Wt1 activity is solely seen in the dilated TAV. Immature vascular smooth muscle cells and absence of pathologic features of cardiovascular ageing in BAV and MFS might explain the observed lack of activation potential in these patients.

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