Abstract 2838: Neopterin is Associated with Plaque Inflammation and Destabilization in Human Coronary Atherosclerotic Lesions
Background: Inflammatory phenomena within vulnerable plaques might explain plaque rupture or erosion and superimposed thrombosis, which leads to vessel closure and ensuing myocardial ischemic injury. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages and serves as an activation marker for monocytes/macrophages. To elucidate the role of neopterin in coronary plaque destabilization, we immunohistochemically studied the presence of neopterin in coronary atherectomy specimens obtained from patients with stable angina (SAP) and unstable angina pectoris (UAP).
Methods: All patients underwent atherectomy of the primary atherosclerotic lesions responsible for SAP (n=24) and UAP (n=23). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, T cells, neutrophils, and neopterin. To identify cell types that stained positive for neopterin, immunodouble staining was also performed.
Results: In 20 of the 23 patients (87%) with UAP, abundant neopterin-positive cells were found at the sites of coronary culprit lesions. However, in 24 lesions from SAP patients, only 11 lesions (46%) showed neopterin positivity. Quantitatively, the percentage of neopterin-positive area was significantly higher (P<0.05) in patients with UAP than in patients with SAP. Moreover, the percentage of the neopterin-positive area showed a significant positive correlation with the number of neutrophils or T cells, respectively (neutrophils, r = 0.64, P<0.0001; T cells, r = 0.67, P<0.0001). Double immunostaining for neopterin and macrophages demonstrated that the vast majority of neopterin-positive cells were macrophages
Conclusions: These results suggest that neopterin plays an important role in the development of inflammatory processes in human coronary plaques. The plaque inflammation induced by neopterin may result in the rapid progression of plaque instability.