title: Immunolocalization of platelet glycoprotein IIb/IIIa and P-selectin, and neutrophil-platelet interaction in human coronary unstable plaques.
abstract: 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.
authors.affiliation: Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ikuta
authors.forename: Takahiko
authors.initials: T
authors.lastname: Naruko
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ikura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ohsawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fukushima
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shirai
authors.forename: Akira
authors.initials: A
authors.lastname: Itoh
authors.forename: Kazuo
authors.initials: K
authors.lastname: Haze
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ehara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shibata
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Suehiro
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*
chemical_list: D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex