| First Author | Ye D | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 395 |
| Issue | 3 | Pages | 387-94 |
| PubMed ID | 20382126 | Mgi Jnum | J:160341 |
| Mgi Id | MGI:4454250 | Doi | 10.1016/j.bbrc.2010.04.027 |
| Citation | Ye D, et al. (2010) Macrophage ABCA5 deficiency influences cellular cholesterol efflux and increases susceptibility to atherosclerosis in female LDLr knockout mice. Biochem Biophys Res Commun 395(3):387-94 |
| abstractText | OBJECTIVES: To determine the role of macrophage ATP-binding cassette transporter A5 (ABCA5) in cellular cholesterol homeostasis and atherosclerotic lesion development. METHODS AND RESULTS: Chimeras with dysfunctional macrophage ABCA5 (ABCA5(-M/-M)) were generated by transplantation of bone marrow from ABCA5 knockout (ABCA5(-/-)) mice into irradiated LDLr(-/-) mice. In vitro, bone marrow-derived macrophages from ABCA5(-M/-M) chimeras exhibited a 29% (P<0.001) decrease in cholesterol efflux to HDL, whereas a 21% (P=0.07) increase in cholesterol efflux to apoA-I was observed. Interestingly, expression of ABCA1, but not ABCG1, was up-regulated in absence of functional ABCA5 in macrophages. To induce atherosclerosis, the transplanted LDLr(-/-) mice were fed a high-cholesterol Western-type diet (WTD) for 6, 10, or 18weeks, allowing analysis of effects on initial as well as advanced lesion development. Atherosclerosis development was not affected in male ABCA5(-M/-M) chimeras after 6, 10, and 18weeks WTD feeding. However, female ABCA5(-M/-M) chimeras did develop significantly (P<0.05) larger aortic root lesions as compared with female controls after 6 and 10weeks WTD feeding. CONCLUSIONS: ABCA5 influences macrophage cholesterol efflux, and selective disruption of ABCA5 in macrophages leads to increased atherosclerotic lesion development in female LDLr(-/-) mice. |
