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Thromb Haemost 2007; 98(05): 1108-1113
DOI: 10.1160/TH07-04-0271
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Elimination of platelet factor 4 (PF4) from platelets reduces atherosclerosis in C57Bl/6 and apoE-/- mice

Bruce S. Sachais
1   Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
,
Tiffany Turrentine
1   Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
,
Jennine M. Dawicki McKenna
1   Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
,
Ann H. Rux
1   Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
,
Daniel Rader
2   Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
,
Anna M. Kowalska
3   Department of Hematology, Children’s Hospital of Philadelphia; Philadelphia, Pennsylvania, USA
4   Center for Medical Biology, Lodz, Poland
› Author Affiliations Financial support: This work was funded in part, by NIH grants 1K08HL004245, 1R01HL078726 and 1R01HL068631, and AHA grant 0255255N.
Further Information

Publication History

Received 13 April 2007

Accepted after resubmission 21 August 2007

Publication Date:
30 November 2017 (online)

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Summary

Activated platelets, which release platelet factor 4 (PF4) are present in patients with atherosclerosis. To date, no direct invivo evidence exists for the involvement of PF4 in atherogenesis. In the current study, we tested the hypothesis that PF4 is atherogenic, and that genetic elimination of PF4 would protect mice from atherosclerosis. We have bred PF4-/- mice onto two athero-susceptible backgrounds, WT-C57Bl/6(WT) and apoE-/- to examine the importance of PF4 in atherogenesis. In order to induce atherosclerosis, WT and PF4-/- mice were fed an atherogenic diet for 30 weeks, while apoE-/- and apoE-/- PF4-/- mice were fed a high-fat Western-style diet for 10 weeks. Examination of lesions in the aortic roots of atherogenic diet fed mice demonstrated reduced atherosclerosis in PF4-/- (20% compared to WT). Examination of apoE-/- mice demonstrated similar changes, with apoE-/- PF4-/- mice demonstrating 37% of the aortic atherosclerotic burden compared to apoE-/- mice. Although we found similar levels of total and non-HDL cholesterol inWT and PF4-/- mice, HDL-cholesterol levels were increased in PF4-/- on both backgrounds. These data demonstrate, for the first time, that the platelet specific chemokine PF4 promotes atherosclerotic lesion development in vivo.

Keywords

Platelets - platelet factor 4 (PF4) - chemokines - atherosclerosis
 

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