Conclusions
Using a panel of molecular tissue markers, the non-dilated BAV patients can be divided into groups susceptible and non-susceptible to aortopathy.
Methods
Ascending aortic wall specimen of BAV (n = 36) and tricuspid aortic valve (TAV) (n = 23), both without and with (>44 mm) dilatation were investigated histologically and immunohistochemically for the expression of markers for vascular remodelling [transforming growth factor (TGF)-β, phosphorylated Smad2, matrix metalloproteinase 9 (MMP9)], cellular differentiation [c-Kit, phosphorylated-c-Kit, hypoxia-inducable factor-1 alpha (HIF1α)] and haemodynamic influences on the aortic wall [endothelial nitric oxide (eNOS)].
Results
All BAV patients showed significantly less inflammation (P < 0.001) and an altered intima/media ratio when compared with TAV patients. The expression of markers of a signalling pathway characteristic for cellular dedifferentiation, as exemplified by the marked expression of c-Kit, phosphorylated c-Kit and HIF1α; in the dilated BAV group was however completely comparable with only a subgroup of the non-dilated BAV (BAb), whereas the remainder of the non-dilated BAV group (BAa) was significantly distinct. This difference between the dilated BAV and BAa was further confirmed in the expression of TGF-β, phosphorylated Smad2, MMP9 and eNOS. Besides the expression pattern, similarity in the dilated BAV and BAb was also noted clinically in the most common variant of commissure position and conjoined raphe of the BAV. Based on these observations, we consider the BAb group a likely candidate for future dilatation as opposed to the BAa group. Conclusions: Using a panel of molecular tissue markers, the non-dilated BAV patients can be divided into groups susceptible and non-susceptible to aortopathy.