Abstract 11572: Association Between Hemoglobin Scavenger Receptor and Heme Oxygenase-1 Related Anti-Inflammatory Mediators in Human Coronary Plaques
Background: Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that is induced by increased cellular stress, such as intraplaque hemorrhage, and helps to maintain physiological homeostasis. Several in-vitro studies have shown that the binding of hemoglobin (Hb) to Hb scavenger receptor (CD163) cells induces HO-1 and the anti-inflammatory mediator interleukin (IL)-10, resulting in an increase in ferritin levels. We previously demonstrated that CD163 is expressed in accumulated macrophages of human coronary unstable plaques (Eur Heart J 30:1844-1852, 2009). In this study, we immunohistochemically examined the relationship between CD163 expression in macrophages and intraplaque hemorrhage, HO-1, IL-10 and ferritin using coronary atherectomy specimens from patients with stable (SAP) or unstable angina pectoris (UAP).
Methods: A total of 67 patients underwent atherectomy of a primary atherosclerotic lesion for SAP (n=33) or UAP (n=34). Samples were stained with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD163, HO-1, IL-10, and ferritin. To identify cell types of HO-1-positive cells, double immunostaining was also performed.
Results: Quantitative analysis demonstrated that the CD163-positive macrophage score and the percentage of glycophorin-A, HO-1, IL-10 and ferritin-positive areas in UAP patients was significantly higher than those in SAP patients (CD163, P<0.005; glycophorin-A, P<0.0001; HO-1, P<0.0001; IL-10, P<0.01; ferritin, P<0.0005). Moreover, the CD163-positive macrophage score was positively correlated with the percentage of HO-1, glycophorin A, IL-10, and ferritin-positive areas (HO-1, r = 0.67, P<0.0001; glycophorin A, r = 0.60, P<0.0001; IL-10, r = 0.39, P<0.005; ferritin, r = 0.61, P<0.0001). Double immunostaining for HO-1 and macrophages revealed that the vast majority of HO-1-positive cells were macrophages.
Conclusions: These findings suggest a positive association between CD163 expression in macrophages and HO-1 related anti-inflammatory mediators in human coronary plaques. Induction of HO-1 by CD163 may be directly involved in the down-regulation of inflammation in patients with UAP.
- © 2011 by American Heart Association, Inc.