Repopulation of Apolipoprotein E Knockout Mice With CCR2-Deficient Bone Marrow Progenitor Cells Does Not Inhibit Ongoing Atherosclerotic Lesion Development

OBJECTIVE—Using bone marrow transplantation, we have previously demonstrated the critical role that hematopoietic CCR2 plays in early atherogenesis. Reconstitution of irradiated apolipoprotein (apo) E3–Leiden mice with CCR2-deficient bone marrow progenitor cells resulted in 86% reduction on overall atherosclerotic lesion development. However, no data on CCR2 in the cause of established atherosclerosis have been reported so far. METHODS AND RESULTS—To study the role of CCR2 in established atherosclerotic lesions, bone marrow progenitor cells harvested from apoE and apoE/CCR2 mice were transplanted into lethally irradiated 16-week-old apoE mice with established atherosclerotic lesions. No significant differences were found in serum total cholesterol and triglycerides levels at different time points after transplantation. At age 16 weeks, lesion size in control apoE mice was 3.28±1.06×10 μm. At 9 weeks after transplantation, apoE→ apoE and apoE/CCR2→ apoE mice had developed significantly larger atherosclerotic lesions (4.49±0.92×10 μm, P