Abstract 564: Enhanced Expression of Hemoglobin Scavenger Receptor in Accumulated Macrophages at the Sites of Coronary Unstable Plaques in Acute Coronary Syndromes
Recent studies suggest that erythrocyte membranes from intraplaque hemorrhage are a source of free cholesterol and have been linked to the pathogenesis of plaque instability. Hemoglobin (Hb)-induced oxidative damage is provided by the protein haptoglobin (Hp), which rapidly and irreversibly binds to extracorpuscular Hb, forming an Hp-Hb complex. In atherosclerotic plaques, the only route for clearance of the Hp-Hb complex is via the macrophage, which is mediated by the membrane receptor CD163. In this study, we immunohistochemically examined the relationship between intraplaque hemorrhage, 4-HNE (4-hydroxy-2- nonenal), an index of lipid peroxidation, and the hemoglobin scavenger receptor (CD163), using coronary atherectomy specimens from patients with stable (SAP) or unstable angina pectoris (UAP). All patients underwent atherectomy of a primary atherosclerotic lesion for SAP (n=39) or UAP (n=35). 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 were quantified using computer-aided planimetry. To identify cell types of CD163-positive cells, double immunostaining was also performed. Quantitative analysis demonstrated that macrophage-, glycophorin A-, and CD163-positive areas in UAP patients were significantly higher than in SAP patients (macrophage, P<0.0001; glycophorin A, P<0.0001; CD163, P<0.0001). Additionally, the 4-HNE-positive macrophage score was significantly (P<0.0001) higher in UAP patients than in SAP patients. Moreover, the percentage of the CD163 -positive area was positively correlated with the 4-HNE-positive macrophage score, and glycophorin A-positive area (4-HNE, R=0.45, P<0.0001; CD163, R=0.57, P<0.0001). Double immunostaining for CD163 and macrophages revealed that the vast majority of CD163-positive cells were macrophages. These findings suggest a positive association between CD 163 expression in macrophages and intraplaque hemorrhage or lipid peroxidation. Intraplaque hemorrhage may lead to increased oxidative stress and contribute to plaque instability.