Abstract 3493: Intraplaque Hemorrhage Induces Oxidative Stress in Human Unstable Coronary Plaques Obtained by Atherectomy
Background: Previous studies have shown that inflammation and oxidative stress in coronary atherosclerotic lesions are related to rapid, progressive plaque destabilization. We have previously demonstrated that an infiltration of neutrophils with positivity for myeloperoxidase, a strong pro-oxidant enzyme, occurs in the culprit lesions of unstable angina pectoris (UAP) patients (Naruko T et al, Circulation 106, 2002). Recent studies have demonstrated that intraplaque hemorrhage is associated with the development of atherosclerotic lesions and plaque instability. Thus, we used immunohistochemical methods to study the correlation between intraplaque hemorrhage and 4-HNE (4-hydroxy-2-nonenal), an oxidative stress-related molecule, in coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP) or UAP.
Methods: All patients underwent atherectomy of a primary atherosclerotic lesion for SAP (n=33) or UAP (n=29). Samples were studied with antibodies against smooth muscle cells, macrophages, neutrophils, glycophorin A (a protein specific for erythrocytes), and 4-HNE. The immunoreactivity of macrophage, neutrophil, glycophorin A, and 4-HNE was quantified using computer-aided planimetry. To identify the colocalization of glycophorin A- positive cells and 4-HNE-positive cells, double immunostaining was also performed.
Results: Quantitative analysis demonstrated that macrophage-, neutrophil-, glycophorin A- and 4-HNE-positive areas in UAP patients were significantly (P<0.001) higher than in SAP patients. Furthermore, we observed that the increase in the percentage of the glycophorin A-positive area showed a significant positive correlation with the 4-HNE-positive area (r=0.82, p<0.0001). Double immunostaining revealed that the 4-HNE-positive cells were colocalized with glycophorin A-positive cells.
Conclusions: These findings suggest a positive association between plaque hemorrhage and 4-HNE localization, which may be an integral part of oxidative stress related to plaque instability in human unstable plaques..