Role of macrophage-derived lipoprotein lipase in lipoprotein metabolism and atherosclerosis

Lipoprotein lipase (LPL) synthesis by macrophages is upregulated in early a therogenesis, implicating the possible involvement of LPL in plaque formati on. However, it is still unclear whether macrophage-derived LPL displays a proatherosclerotic or an antiatherosclerotic role in atherosclerotic lesion development. In this study, the role of macrophage-derived LPL on lipid me tabolism and atherosclerosis was assessed in vivo by transplantation of LPL -deficient (LPL-/-) and wild-type (LPL+/+) bone marrow into C57BL/6 mice. E ight weeks after bone marrow transplantation (BMT), serum cholesterol level s in LPL-/- -->,C57BL/6 mice were reduced by 8% compared with those in LPL/+-->C57BL/6 mice (P<0.05, n=16), whereas triglycerides were increased by 3 3% (P<0.05, n=16). Feeding the mice a high-cholesterol diet increased serum cholesterol levels in LPL-/-->C57BL/6 and LPL+/+-->C57BL/6 mice 5-fold and 9-fold, respectively, resulting in a difference of approximate to 50% (P<0 .01) after 3 months on the diet. No effects on triglyceride levels were obs erved under these conditions. Furthermore, serum apolipoprotein E levels we re reduced by 50% in the LPL-/-->C57BL/6 mice compared with controls under both dietary conditions. After 3 months on a high-cholesterol diet, the ath erosclerotic lesion area in LPL-/-->C57BL/6 mice was reduced by 52% compare d with controls. It can be concluded that macrophage-derived LPL plays a si gnificant role in the regulation of serum cholesterol, apolipoprotein E, an d atherogenesis, suggesting that specific blockade of macrophage LPL produc tion may be beneficial for decreasing atherosclerotic lesion development.