Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters

Stephanie Pitsilos; Jennifer Hunt; Emile R. Mohler; Anand M. Prabhakar; Mortimer Poncz; Jennine Dawicki; Tigran Z. Khalapyan; Megan L.Wolfe; Ronald Fairman; Marc Mitchell; Jeffrey Carpenter; Michael A. Golden; Douglas B. Cines; Bruce S. Sachais

doi:10.1160/TH03-02-0069

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(06): 1112-1120
DOI: 10.1160/TH03-02-0069

Platelets and Blood Cells

Schattauer GmbH

Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters

Stephanie Pitsilos

¹Departments of Pathology and Laboratory Medicine, Univ. of Pennsylvania, Philadelphia, USA

,

Jennifer Hunt

²Department of Pathology and Laboratory Medicine, University of Pittsburgh, Pittsburgh, USA

,

Emile R. Mohler

³Departments of Cardiology, Univ. of Pennsylvania, Philadelphia, USA

,

Anand M. Prabhakar

¹Departments of Pathology and Laboratory Medicine, Univ. of Pennsylvania, Philadelphia, USA

,

Mortimer Poncz

⁴Departments of Pediatrics, Univ. of Pennsylvania, Philadelphia, USA

,

Jennine Dawicki

¹Departments of Pathology and Laboratory Medicine, Univ. of Pennsylvania, Philadelphia, USA

,

Tigran Z. Khalapyan

³Departments of Cardiology, Univ. of Pennsylvania, Philadelphia, USA

,

Megan L.Wolfe

³Departments of Cardiology, Univ. of Pennsylvania, Philadelphia, USA

,

Ronald Fairman

⁵Departments of Surgery, Univ. of Pennsylvania, Philadelphia, USA

,

Marc Mitchell

⁵Departments of Surgery, Univ. of Pennsylvania, Philadelphia, USA

,

Jeffrey Carpenter

⁵Departments of Surgery, Univ. of Pennsylvania, Philadelphia, USA

,

Michael A. Golden

⁵Departments of Surgery, Univ. of Pennsylvania, Philadelphia, USA

,

Douglas B. Cines

¹Departments of Pathology and Laboratory Medicine, Univ. of Pennsylvania, Philadelphia, USA

,

Bruce S. Sachais

¹Departments of Pathology and Laboratory Medicine, Univ. of Pennsylvania, Philadelphia, USA

› Author Affiliations

Abstract

Summary

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 χ²-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 athero-sclerotic vascular lesions. These studies support the rationale for the chronic use of anti-platelet therapy in patients at risk for developing symptomatic atherosclerosis.

Keywords

Atherosclerosis - platelet activation markers - vasculopathies - macrophage / phagocytosis

Full Text

References

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