Aim: This immunohistochemical investigation was to analyze the relationship between platelet activation/aggregation, inflammatory cell infiltration, the differentiation state of neointimal smooth muscle cells (SMCs), expression of platelet-derived growth factor (PDGF), and endothelial cell regeneration at sites of bare-metal stents (BMS) in patients with acute coronary syndrome (ACS).
Methods: Sixteen coronary arteries after stenting were obtained at autopsy from ACS patients. Serial frozen sections were stained with antibodies against SMCs (1A4, HHF-35, CGA-7), macrophages, neutrophils, endothelial cells, GP IIb/IIIa, P-selectin, PDGF-B, and PDGF-beta receptor.
Results: Up to 12 days after BMS, the stent sites contained P-selectin-positive activated platelets with neutrophil infiltration. From 24 to 55 days after BMS, parts of the platelet thrombi were still positive for P-selectin, and infiltration of neutrophils and macrophages was also found. Neointimal SMCs at these stages stained positive with 1A4 but negative with CGA-7, and PDGF-B and PDGF-beta receptor were expressed in macrophages and SMCs. At sites from 3 months onward, platelet thrombi and neutrophil infiltration were not detected, and the neointima contained increased numbers of highly differentiated SMCs with CGA-7 positivity. The P-selectin-positive area was positively correlated with the neutrophil count and macrophage-positive area (neutrophils, r=0.86, p<0.0005; macrophage, r=0.66, p<0.05). In contrast, the P-selectin-positive area was negatively correlated with the HHF-35-positive area and CGA-7-positive area (HHF-35, r=-0.90, p<0.0001; CGA-7, r=-0.82, p<0.005).
Conclusion: These observations suggest that P-selectin-positive platelet thrombi in the neointima are positively associated with the inflammatory cell infiltration and reversely associated with the phenotypic redifferentiation of neointimal SMCs after BMS in ACS patients.