4-hydroxy-2-nonenal and Aortic-Valve-Stenosis

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.. 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.. 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).. 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.

Topics: Aged; Aged, 80 and over; Aldehydes; Aortic Valve Stenosis; Female; Humans; Immunohistochemistry; Male; Oxidative Stress; Platelet Endothelial Cell Adhesion Molecule-1

The aim of the present study was to analyze if LDL particles trapped in stenotic aortic valve tissue undergo oxidative modification. Degenerative aortic stenosis affects >3% of the population >75 years of age in the Western world. Recent studies have revealed the presence of a chronic inflammatory process similar to what has been described in other degenerative diseases such as atherosclerosis. However, the underlying disease mechanisms of degenerative aortic stenosis still remain largely unknown. Six tricuspid stenotic valves, obtained at valve replacement, were compared with 3 control valves collected from hearts taken out during transplantation. The stenotic valves and the control valves were examined by immunohistochemistry, using antibodies against apoB, 4-hydroxynonenal-modified LDL, leukocytes, and HLA-DR. All valves were also stained with oil red O for neutral lipids. Extracellular neutral lipids were found in all stenotic valves, extending from the bases along the fibrosa layer. This lipid colocalized with apoB- and 4-hydroxynonenal-modified LDL immunoreactivity. 4-Hydroxynonenal-modified LDLs were present around calcium deposits, subendothelially, and in the deeper layer of the fibrosa. There was also a colocalization with macrophages, T lymphocytes, and HLA-DR expression. Control valves had a thin area of neutral lipid accumulation, a small amount of apoB, but no signs of inflammation. A distinct colocalization between oxidized LDLs, T-lymphocyte accumulation, and calcium deposits suggests that oxidized lipids may play a role in the disease process.

Topics: Adult; Age Factors; Aged; Aldehydes; Aortic Valve Stenosis; Apolipoproteins B; Azo Compounds; Calcinosis; Calcium; Coloring Agents; HLA-DR Antigens; Humans; Inflammation; Lipids; Lipoproteins, LDL; Macrophages; Middle Aged; T-Lymphocytes; Tricuspid Valve Stenosis