| First Author | Zhu L | Year | 2016 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 36 |
| Issue | 8 | Pages | 1483-95 |
| PubMed ID | 27365402 | Mgi Jnum | J:246699 |
| Mgi Id | MGI:5920097 | Doi | 10.1161/ATVBAHA.116.307736 |
| Citation | Zhu L, et al. (2016) Loss of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 Confers Resistance to the Antiatherogenic Effects of Tumor Necrosis Factor-alpha Inhibition. Arterioscler Thromb Vasc Biol 36(8):1483-95 |
| abstractText | OBJECTIVE: Antiatherosclerotic effects of tumor necrosis factor-alpha (TNF-alpha) blockade in patients with systemic inflammatory states are not conclusively demonstrated, which suggests that effects depend on the cause of inflammation. Macrophage LRP1 (low-density lipoprotein receptor-related protein 1) and apoE contribute to inflammation through different pathways. We studied the antiatherosclerosis effects of TNF-alpha blockade in hyperlipidemic mice lacking either LRP1 (MPhiLRP1(-/-)) or apoE from macrophages. APPROACH AND RESULTS: Lethally irradiated low-density lipoprotein receptor (LDLR)(-/-) mice were reconstituted with bone marrow from either wild-type, MPhiLRP1(-/-), apoE(-/-) or apoE(-/-)/MPhiLRP1(-/-)(DKO) mice, and then treated with the TNF-alpha inhibitor adalimumab while fed a Western-type diet. Adalimumab reduced plasma TNF-alpha concentration, suppressed blood ly6C(hi) monocyte levels and their migration into the lesion, and reduced lesion cellularity and inflammation in both wild-type-->LDLR(-/-) and apoE(-/-)-->LDLR(-/-) mice. Overall, adalimumab reduced lesion burden by 52% to 57% in these mice. Adalimumab reduced TNF-alpha and blood ly6C(hi) monocyte levels in MPhiLRP1(-/-)-->LDLR(-/-) and DKO-->LDLR(-/-) mice, but it did not suppress ly6C(hi) monocyte migration into the lesion or atherosclerosis progression. CONCLUSIONS: Our results show that TNF-alpha blockade exerts antiatherosclerotic effects that are dependent on the presence of macrophage LRP1. |
