| First Author | Gupta S | Year | 1997 |
| Journal | J Clin Invest | Volume | 99 |
| Issue | 11 | Pages | 2752-61 |
| PubMed ID | 9169506 | Mgi Jnum | J:40921 |
| Mgi Id | MGI:892640 | Doi | 10.1172/JCI119465 |
| Citation | Gupta S, et al. (1997) IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest 99(11):2752-61 |
| abstractText | The early colocalization of T cells and the potent immunostimulatory cytokine IFN-gamma to atherosclerotic lesions suggest that the immune system contributes to atherogenesis. Since mice with a targeted disruption of the apoE gene (apoE 0 mice) develop profound atherosclerosis, we examined the role of IFN-gamma in this process. First, the presence of CD4(+) and CD8(+) cells, which secrete lesional IFN-gamma, was documented in apoE 0 atheromata. Then, the apoE 0 mice were crossed with IFN-gamma receptor (IFNgammaR) 0 mice to generate apoE 0/IFNgammaR 0 mice. Compared to the apoE 0 mice, the compound knock-out mice exhibited a substantial reduction in atherosclerotic lesion size, a 60% reduction in lesion lipid accumulation, a decrease in lesion cellularity, but a marked increase in lesion collagen content. Evaluation of the plasma lipoproteins showed that the compound knockout mice had a marked increase in potentially atheroprotective phospholipid/apoA-IV rich particles as well. This correlated with an induction of hepatic apoA-IV transcripts. These observations suggest that IFN-gamma promotes and modifies atherosclerosis through both local effects in the arterial wall as well as a systemic effect on plasma lipoproteins. Therefore, therapeutic inhibition of IFN-gamma signaling may lead to the formation of more lipid-poor and stable atheromata. |
