Immunolocalization of platelet glycoprotein IIb/IIIa and P-selectin, and neutrophil-platelet interaction in human coronary unstable plaques.

Platelet aggregation at the site of plaque rupture or erosion is a dominant feature in the pathophysiology of plaque destabilization. To elucidate the role of glycoprotein (GP) IIb/IIIa in coronary plaque destabilization, we immunohistochemically studied the presence of GP IIb/IIIa in coronary atherectomy specimens obtained from patients with stable angina (SAP) and unstable angina pectoris (UAP). Moreover, we immunohistochemically investigated the presence of P-selectin, which is known to be a marker of platelet activation, in these specimens. All these patients underwent atherectomy at primary atherosclerotic lesions responsible for SAP (n=25) and UAP (n=23). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, neutrophils, endothelial cells, GP IIb/IIIa and P-selectin. Immunoreactive positive areas for GP IIb/IIIa, P-selectin, and macrophages, respectively, were calculated using computer-aided planimetry, and numbers of neutrophils were also counted. In the culprit lesions of UAP patients, 17 of the 23 lesions (74%) contained GP IIb/IIIa positive platelet thrombi, and all these platelet thrombi were positive for P-selectin. In contrast, in the lesions of SAP patients, 3 of the 25 lesions (12%) showed staining positivity for GP IIb/IIIa and P-selectin. Quantitatively, the percentage of GP IIb/IIIa- and P-selectin-positive area was significantly higher (GP IIb/IIIa, P<0.0005; P-selectin, P<0.0001) in patients with UAP than in patients with SAP. The number of neutrophils was significantly higher (P<0.0005) in patients with UAP than in patients with SAP. Moreover, the percentage of GP IIb/IIIa-positive area showed a significant positive correlation with the number of neutrophils (r=0.66, p<0.0001). These findings strongly suggest that platelet activation and aggregation, leading to formation of platelet thrombi, and the interaction between activated platelets and neutrophils play a pivotal role in the pathogenesis of plaque destabilization in human coronary atherosclerotic lesions.