Impact of Macrophage Inflammatory Protein-1α Deficiency on Atherosclerotic Lesion Formation, Hepatic Steatosis, and Adipose Tissue Expansion

Macrophage inflammatory protein-1α (CCL3) plays a well-known role in infectious and viral diseases; however, its contribution to atherosclerotic lesion formation and lipid metabolism has not been determined. Low density lipoprotein receptor deficient (LDLR(−/−)) mice were transplanted with bone marrow from CCL3(−/−) or C57BL/6 wild type donors. After 6 and 12 weeks on western diet (WD), recipients of CCL3(−/−) marrow demonstrated lower plasma cholesterol and triglyceride concentrations compared to recipients of C57BL/6 marrow. Atherosclerotic lesion area was significantly lower in female CCL3(−/−) recipients after 6 weeks and in male CCL3(−/−) recipients after 12 weeks of WD feeding (P<0.05). Surprisingly, male CCL3(−/−) recipients had a 50% decrease in adipose tissue mass after WD-feeding, and plasma insulin, and leptin levels were also significantly lower. These results were specific to CCL3, as LDLR(−/−) recipients of monocyte chemoattractant protein(−/−) (CCL2) marrow were not protected from the metabolic consequences of high fat feeding. Despite these improvements in LDLR(−/−) recipients of CCL3(−/−) marrow in the bone marrow transplantation (BMT) model, double knockout mice, globally deficient in both proteins, did not have decreased body weight, plasma lipids, or atherosclerosis compared with LDLR(−/−) controls. Finally, there were no differences in myeloid progenitors or leukocyte populations, indicating that changes in body weight and plasma lipids in CCL3(−/−) recipients was not due to differences in hematopoiesis. Taken together, these data implicate a role for CCL3 in lipid metabolism in hyperlipidemic mice following hematopoietic reconstitution.