A decline in platelet activation and inflammatory cell infiltration is associated with the phenotypic redifferentiation of neointimal smooth muscle cells after bare-metal stent implantation in acute coronary syndrome.
OBJECTIVE
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).


CONCLUSIONS
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.
Nakagawa
Masashi
M
Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Osaka, Japan.
Naruko
Takahiko
T
Ikura
Yoshihiro
Y
Komatsu
Ryushi
R
Iwasa
Yoko
Y
Kitabayashi
Chizuko
C
Inoue
Takeshi
T
Itoh
Akira
A
Yoshiyama
Minoru
M
Ueda
Makiko
M
D054058:Acute Coronary Syndrome / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008670:Metals / Q000494:pharmacology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D019007:P-Selectin / Q000378:metabolism; D010641:Phenotype; D015539:Platelet Activation; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015607:Stents; D017539:Tunica Intima / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D008670:Metals; D019007:P-Selectin; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta