Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice

The role of macrophage lipoprotein lipase (LPL) expression in atherosclerot ic lesion formation was examined in low density lipoprotein receptor (LDLR- /-) mice using dietary conditions designed to induce either fatty streak le sions or complex atherosclerotic lesions. First, LDLR-/- mice chimeric for macrophage LPL expression were created by transplantation of lethally irrad iated female LDLR-/- mice with LPL-/- (n = 12) or LPL+/+ (n = 14) fetal liv er cells as a source of hematopoietic cells. To induce fatty streak lesions , these mice were fed a Western diet for 8 weeks, resulting in severe hyper cholesterolemia, There were no differences in plasma postheparin LPL activi ty, serum lipid levels, or lipoprotein distribution between these two group s. The mean lesion area in the proximal aorta in LPL-/- --> LDLR-/- mice wa s significantly reduced by 33% compared with LPL+/+ --> LDLR-/- mice, and a similar reduction (38%) in lesion area was found by en face analysis of th e aortae. To induce complex atherosclerotic lesions, female LDLR-/- mice we re lethally irradiated, transplanted with LPL-/-(n = 14), LPL+/- (n = 13), or LPL+/+ (n = 14) fetal liver cells, and fed the Western diet for 19 weeks . Serum cholesterol and triglyceride levels did not differ between the thre e groups. After 19 weeks of diet, the lesions in the proximal aorta were co mplex with relatively few macrophages expressing LPL protein and mRNA in LP L+/+ --> LDLR-/- mice. Analysis of cross-sections of the proximal aorta dem onstrated no differences in the extent of lesion area between the groups, w hereas en face analysis of the aortae revealed a dose-dependent effect of m acrophage LPL on mean aortic lesion area in LPL-/- --> LDLR-/-, LPL-/+ --> LDLR-/-, and LPL+/+ --> LDLR-/- mice (1.8 +/- 0,2%, 3.5 +/- 0.5% and 5.9 +/ - 0,8%, respectively). Taken together, these data indicate that macrophage LPL expression in the artery wall promotes atherogenesis during foam cell l esion formation, but this impact may be limited to macrophage-rich lesions.