Relationship between oxidative stress and aortic valve stenosis in humans: an immunohistochemical study.

BACKGROUND: Oxidative stress contributes to plaque formation and the destabilization of coronary atherosclerotic lesions. It has been reported that disease processes and clinical risk factors of aortic valve stenosis (AS) are similar to those of atherosclerosis. In this study, we immunohistochemically examined the expression of 4-hydroxy-2-nonenal (4-HNE), an oxidative stress-related molecule, by using surgically resected aortic valve specimens from AS patients. METHODS: The study was conducted using aortic valve specimens, surgically obtained from 24 patients with severe AS undergoing aortic valve replacement. We immunohistochemically investigated frozen aortic valve samples with antibodies against smooth muscle cells, macrophages, CD31 and 4-HNE. RESULTS: Morphometric analysis showed that the percentage of the macrophage-positive area and the number of CD31-positive microvessels were significantly higher in AS patients than those in reference cases (macrophages, p < 0.005 and CD31, p < 0.0001). Furthermore, the 4-HNE-positive macrophage score was also significantly higher in AS patients than in reference cases (p < 0.005). CONCLUSIONS: 4-HNE was expressed in the stenotic aortic valves in patients with severe AS, suggesting a close relationship between oxidative stress and the progression of calcific AS.