| First Author | Out R | Year | 2006 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 26 |
| Issue | 10 | Pages | 2295-300 |
| PubMed ID | 16857950 | Mgi Jnum | J:128052 |
| Mgi Id | MGI:3765407 | Doi | 10.1161/01.ATV.0000237629.29842.4c |
| Citation | Out R, et al. (2006) Macrophage ABCG1 deletion disrupts lipid homeostasis in alveolar macrophages and moderately influences atherosclerotic lesion development in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 26(10):2295-300 |
| abstractText | OBJECTIVE: ABCG1 has recently been identified as a facilitator of cellular cholesterol and phospholipid efflux to high-density lipoprotein (HDL). Its expression in macrophages is induced during cholesterol uptake in macrophages and by liver X receptor (LXR). The role of macrophage ABCG1 in atherosclerotic lesion development is, however, still unknown. METHODS AND RESULTS: To assess the role of macrophage ABCG1 in atherosclerosis, we generated low-density lipoprotein (LDL) receptor knockout (LDLr-/-) mice that are selectively deficient in macrophage ABCG1 by using bone marrow transfer (ABCG1-/- --> LDLr-/-). Peritoneal macrophages isolated from donor ABCG1-/- mice exhibited a 22% (P=0.0007) decrease in cholesterol efflux to HDL. To induce atherosclerosis, transplanted mice were fed a high-cholesterol diet containing 0.25% cholesterol and 15% fat for 6 and 12 weeks. Serum lipid levels and lipoprotein profiles did not differ significantly between ABCG1-/- --> LDLr-/- mice and controls. In lungs of ABCG1-/- --> LDLr-/- mice a striking accumulation of lipids was observed in macrophages localized to the subpleural region. After 6 weeks of high-cholesterol diet feeding the atherosclerotic lesion size was 49+/-12x10(3) microm2 for ABCG1+/+ --> LDLr-/- mice versus 65+/-15x103 microm2 for ABCG1-/- --> LDLr-/- mice and after 12 weeks of high-cholesterol diet feeding 124+/-17x10(3) microm2 for ABCG1+/+ --> LDLr-/- mice versus 168+/-17x10(3) microm2 for ABCG1-/- --> LDLr-/- mice. Atherosclerotic lesion size depended on both time and the macrophage ABCG1 genotype (P=0.038 by 2-way ANOVA, n > or = 8), indicating a moderately 33% to 36% increase in lesion formation in the absence of macrophage ABCG1. CONCLUSIONS: Macrophage ABCG1 deficiency does lead to heavy lipid accumulation in macrophages of the lung, and also a moderately significant effect on atherosclerotic lesion development was observed. |
