Abstract 13403: Enhanced Expression of Hemoglobin Scavenger Receptor and Heme Oxygenase-1 is Associated With Aortic Valve Stenosis in Patients Undergoing Hemodialysis
Background: A high prevalence and a rapid progression of aortic valve stenosis (AS) in patients undergoing hemodialysis (HD) has been reported. Under these conditions, intraleaflet hemorrhage of the aortic valve may be related to the development of AS in HD patients. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that is induced by intraplaque hemorrhage and degrades free heme and releases ferrous iron. In vitro studies have shown that binding of hemoglobin (Hb) to Hb scavenger receptor (CD163) induces HO-1. We immunohistochemically examined the relationship between intraleaflet hemorrhage, neovascularization, CD163 and HO-1 using valve specimens from AS patients undergoing HD.
Methods: The study population consisted of 26 HD patients and 25 non-HD patients with severe AS who underwent aortic valve replacement. Frozen aortic valve samples surgically obtained from AS patients were stained immunohistochemically with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD31, CD163 and HO-1. To identify CD163- or HO-1-positive cells, we also performed double immunostaining.
Results: Morphometric analysis demonstrated that the CD163-positive macrophage score, the number of CD31-positive microvessels, and the percentage of glycophorin A and HO-1-positive areas were significantly higher in HD than in non-HD patients (CD163-positive macrophage score, P<0.0001; CD31-positive microvessels, P<0.0001; glycophorin A, P<0.0001; and HO-1, P<0.0001). Furthermore, the CD163-positive macrophage score was positively correlated with glycophorin A, HO-1-positive area and the number of CD31-positive microvessels (glycophorin A, R=0.67, P<0.0001; HO-1, R=0.50; P<0.0005; microvessels, R=0.38; P<0.01). Double immunostaining for CD163 or HO-1 and macrophages revealed that the majority of CD163- or HO-1-positive cells were macrophages.
Conclusions: These findings suggest a positive association among intraleaflet hemorrhage, neovascularization and enhanced expression of CD163 and HO-1 in aortic valve in AS patients undergoing HD, which contributes to rapid progression of AS in these patients.
- © 2013 by American Heart Association, Inc.