Enhanced expression of neopterin in valve tissue of bicuspid aortic stenosis.

Background: Aortic valve stenosis (AS) occurs in bicuspid aortic valve (BAV) patients at a relatively young age compared to tricuspid aortic valve (TAV) patients. However, the underlying cause of this phenomenon remains unknown. Neopterin, which is a by-product of the guanosine triphosphate (GTP) pathway, enhances the oxidative potential of reactive oxygen species. To clarify the role of neopterin in the aortic valve, we immunohistochemically studied the presence of neopterin in aortic valve specimens from patients with AS harboring either TAV or BAV. Methods: Frozen aortic valve samples were surgically obtained from 68 patients with severe AS with TAV (n=34) and BAV (n=34). Normal aortic valves were obtained from cadavers who died of non-cardiovascular causes as controls (n=9). Samples were immunohistochemically stained with antibodies against smooth muscle cells, macrophages, T lymphocytes, neopterin, and 4-hydroxy-2-nonenal (4-HNE). Results: Quantitative analysis showed that the percentage of macrophages, 4-HNE- and neopterin-positive macrophage score, and the number of T lymphocytes were significantly higher in BAV patients than in TAV patients (macrophages, P=0.013; T lymphocytes, P=0.011; neopterin, P<0.001; 4-HNE, P=0.008). Double immunostaining for neopterin and macrophages demonstrated that most neopterin-positive cells were macrophages in BAV patients. Conclusions: Neopterin accumulation in macrophages may increase oxidative stress and contribute to the early onset of AS in BAV.