Endothelial nitric oxide synthase in bicuspid aortic valve disease

The pathogenesis of ascending aortic dilatation in the presence of a bicuspid valve is discussed controversially. Recent experimental evidence suggests that the expression of endothelial nitric oxide synthase (eNOS) may have an influence on aortic valve anatomy and aneurysmal dilatation of the aorta. We investigated the relationship among eNOS expression, valve anatomy, and aortic dilatation in the human aortic wall.

Aortic wall specimens from 39 patients with aortic valve disease (bicuspid, n = 17; tricuspid, n = 22) were studied. The functional aortic valve pathology was regurgitation (n = 22), stenosis (n = 10), and combined aortic valve disease (n = 7). The specimens were obtained intraoperatively from the aortic wall above the noncoronary sinus. The eNOS protein expression was quantified by western blot analysis after immunoprecipitation from tissue lysates. The eNOS levels were analyzed for correlation with valve anatomy and ascending aortic diameters.

The eNOS protein expression of aortic endothelial cells was significantly lower in patients with bicuspid as compared with tricuspid aortic valves (4,615 +/- 489 vs 6,275 +/- 442; p = 0.017). In bicuspid aortic valves there was a significant correlation between eNOS expression and maximum aortic diameter (r = -0.530; p = 0.029) or sinotubular diameter (r = -0.520; p = 0.033). In patients with tricuspid aortic valves, no significant correlation between aortic size and eNOS expression was found.

Our results show an association between eNOS levels and aortic valve anatomy as well as aneurysm formation in patients with bicuspid aortic valves.