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