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Updated: Jul 10, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Elimination of platelet factor 4 (PF4) from platelets reduces atherosclerosis in C57Bl/6 and apoE-/- mice
Bruce S Sachais1, Tiffany Turrentine, Jennine M Dawicki McKenna
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. sachais@mail.med.upenn.edu
Insights
Platelet factor 4 (PF4) promotes atherosclerosis. Genetic removal of PF4 reduced atherosclerotic lesion development in mice, indicating PF4
Area of Science:
- Cardiovascular Research
- Immunology
- Platelet Biology
Background:
- Activated platelets release platelet factor 4 (PF4), a chemokine implicated in various inflammatory conditions.
- Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.
- Direct in-vivo evidence linking PF4 to the development of atherosclerosis has been lacking.
Purpose of the Study:
- To investigate the role of PF4 in the development of atherosclerosis.
- To determine if genetic elimination of PF4 confers protection against atherosclerosis in vivo.
- To test the hypothesis that PF4 is atherogenic.
Main Methods:
- Generation of PF4-deficient (PF4-/-) mice on both wild-type (WT) and apolipoprotein E-deficient (apoE-/-) backgrounds.
- Induction of atherosclerosis using an atherogenic diet in WT and PF4-/- mice for 30 weeks.
- Induction of atherosclerosis using a high-fat Western-style diet in apoE-/- and apoE-/- PF4-/- mice for 10 weeks.
- Quantification of atherosclerotic lesions in the aortic roots.
Main Results:
- PF4-/- mice exhibited a 20% reduction in atherosclerotic lesions compared to WT mice on an atherogenic diet.
- ApoE-/- PF4-/- mice showed a 37% reduction in aortic atherosclerotic burden compared to apoE-/- mice.
- PF4 deficiency led to increased HDL-cholesterol levels without affecting total or non-HDL cholesterol.
Conclusions:
- Platelet factor 4 (PF4) plays a significant role in promoting atherosclerotic lesion development.
- Genetic elimination of PF4 provides protection against atherosclerosis in vivo.
- PF4 may represent a novel therapeutic target for atherosclerosis.
Abstract:
Activated platelets, which release platelet factor 4 (PF4) are present in patients with atherosclerosis. To date, no direct in-vivo 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 in WT 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.
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