title: Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters.
abstract: Emerging evidence supports a role for platelets in the progression of atherosclerosis in addition to an involvement in thrombotic vascular occlusion. Platelet Factor 4 (PF4), a chemokine released by activated platelets, stimulates several pro-atherogenic processes. Therefore, we examined the localization of PF4 and the homologous protein, Neutrophil Activating Protein-2 (NAP-2) in lesions representing the evolution of human atherosclerotic plaques. Carotid plaques from 132 patients with critical carotid stenosis and 6 autopsy specimens were studied. Clinical, histologic and immunohistochemical data were analyzed using a chi(2)-test. PF4 was detected in the cytoplasm of luminal and neovascular endothelium, in macrophages and in regions of plaque calcification. The presence of PF4 in macrophages and neovascular endothelium correlated with lesion grade (p = 0.004; p = 0.044). Staining of macrophages for PF4 correlated with the presence of symptomatic atherosclerotic disease (p = 0.028). In early lesions, PF4 was commonly found in macrophages of early lesions (Grade I/II), whereas NAP-2 was rarely present. In conclusion, correlation between PF4 deposition, lesion severity and symptomatic atherosclerosis suggests that persistent platelet activation may contribute to the evolution of atherosclerotic vascular lesions. These studies support the rationale for the chronic use of anti-platelet therapy in patients at risk for developing symptomatic atherosclerosis.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Pitsilos
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hunt
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.forename: Anand M
authors.initials: AM
authors.lastname: Prabhakar
authors.forename: Mortimer
authors.initials: M
authors.lastname: Poncz
authors.forename: Jennine
authors.initials: J
authors.lastname: Dawicki
authors.forename: Tigran Z
authors.initials: TZ
authors.lastname: Khalapyan
authors.forename: Megan L
authors.initials: ML
authors.lastname: Wolfe
authors.forename: Ronald
authors.initials: R
authors.lastname: Fairman
authors.forename: Marc
authors.initials: M
authors.lastname: Mitchell
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Carpenter
authors.forename: Michael A
authors.initials: MA
authors.lastname: Golden
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cines
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Sachais
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000209:etiology / Q000378:metabolism*; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D010978:Platelet Factor 4 / Q000032:analysis / Q000378:metabolism*; D012720:Severity of Illness Index; D001620:beta-Thromboglobulin
chemical_list: C061615:PPBP protein, human; D010455:Peptides; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4