Abstract 16475: Enhanced Expression of Hemoglobin Scavenger Receptor is Associated With Aortic Valve Stenosis in Patients With Bicuspid Aortic Valve

• Published in: Circulation (New York, N.Y.) Vol. 134; no. Suppl_1 Suppl 1; p. A16475
• Main Authors: Matsushita, Tsukasa, Mastumura, Yoshiki, Simeno, Kenji, Mastumoto, Ryo, Abe, Yukio, Kamimori, Kimio, Naruko, Takahiko, Sugioka, Kenichi, Nakagawa, Masashi, Yoshiyama, Minoru Yoshiyama, Ueda, Makiko
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 11.11.2016
• ISSN: 0009-7322; 1524-4539

BackgroundRecent studies have shown that intraleaflet hemorrhage occurs in aortic valve leaflets and is associated with accelerated progression of aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) compared to patients with tricuspid aortic valve (TAV). Hemoglobin (Hb)-induced oxidative damage is caused by the protein haptoglobin (Hp), which rapidly and irreversibly binds to extracorpuscular Hb, forming an Hp-Hb complex. In aortic valve leaflets, the only route for clearance of the Hp-Hb complex is via macrophages, mediated by the membrane receptor CD163. In this study, we immunohistochemically examined the relationship between intraleaflet hemorrhage, 4-HNE (4-hydroxy-2-nonenal), an index of lipid peroxidation, and CD163 in aortic valve specimens from AS patients with either TAV or BAV.MethodsFrozen aortic valve samples were obtained surgically from AS patients with either TAV (n=35) or BAV (n=34). Samples were stained with antibodies against smooth muscle cells, macrophages, glycophorin A (a protein specific to erythrocyte membranes), CD163 and 4-HNE. The immunoreactivity of macrophages, glycophorin A, CD163, and 4-HNE was quantified using computer-aided planimetry. To identify cell types of CD163-positive cells, double immunostaining was also performed.ResultsQuantitative analysis demonstrated that macrophage-, glycophorin A-, and CD163-, and 4-HNE-positive areas in BAV patients were significantly higher than those in TAV patients (macrophage, P<0.001; glycophorin A, P<0.0001; CD163, P<0.0005; 4-HNE, P<0.05). Moreover, the percentage of the CD163 -positive area was positively correlated with the 4-HNE-positive area, and glycophorin A-positive area (4-HNER=0.62, P<0.0001; glycophorin AR=0.52, P<0.0001). Double immunostaining for CD163 and macrophages revealed that the vast majority of CD163-positive cells were macrophages.ConclusionsThese findings indicate a positive association between CD163 expression in macrophages and intraleaflet hemorrhage and lipid peroxidation. Intraleaflet hemorrhage, which increases oxidative stress, may contribute to rapid AS progression in BAV patients.