| First Author | Xie P | Year | 2014 |
| Journal | Biochim Biophys Acta | Volume | 1841 |
| Issue | 12 | Pages | 1683-90 |
| PubMed ID | 25178844 | Mgi Jnum | J:230478 |
| Mgi Id | MGI:5760124 | Doi | 10.1016/j.bbalip.2014.08.014 |
| Citation | Xie P, et al. (2014) Transgenic CGI-58 expression in macrophages alleviates the atherosclerotic lesion development in ApoE knockout mice. Biochim Biophys Acta 1841(12):1683-90 |
| abstractText | Comparative Gene Identification-58 (CGI-58), as an adipose triglyceride lipase (ATGL) activator, strongly in- creases ATGL-mediated triglyceride (TG) catabolism. Previous studies have shown that CGI-58 affects intestinal cholesterol homeostasis independently of ATGL activity. Therefore, we hypothesized that CGI-58 was involved in macrophage cholesterol metabolism and consequently atherosclerotic lesion formation. Here, we generated macrophage-specific CGI-58 transgenic mice (Mac-CGI-58 Tg) using an SRA promoter, which was further mated with ApoE-/- mice to create litters of CGI-58 Tg/ApoE-/- mice. These CGI-58 Tg/ApoE-/- mice exhibited an anti-atherosclerosis phenotype compared with wild type (WT) controls (CGI-58 WT/ApoE-/-), illustrated by less plaque area in aortic roots. Moreover, macrophage-specific CGI-58 overexpression in mice resulted in upregulated levels of plasma total cholesterol and HDL-cholesterol. Consequently, higher expression levels of PPARa, PPARgamma, LXRalpha, ABCA1, and ABCG1 were detected in macrophages from CGI-58 Tg/ApoE-/- mice compared to CGI-58 WT/ApoE-/- counterparts, which were accompanied by elevated macrophage cholesterol efflux toward HDL and Apo A1. Nevertheless, serum levels of TNF-alpha and IL-6 were reduced by macrophage-specific CGI-58 overexpression. Finally, bone marrow (BM) transplantation experiments further revealed that ApoE-/- mice reconstituted with Mac-CGI-58 Tg BM cells (ApoE-/-Tg-BM chimera) displayed a significant reduction of atherosclerosis lesions compared with control mice reconstituted with Mac-CGI-58 WT BM cells (ApoE-/-/WT-BM chimera). Collectively, these data strongly suggest that CGI-58 overexpression in macrophages may protect against atherosclerosis development in mice. |
