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- W3172989968 abstract "Abstract Purpose Interleukin (IL)-1β plays an important role in the atherosclerosis pathogenesis. We aimed to investigate the effect of anakinra, a recombinant human IL-1 receptor antagonist, on the progression of atherosclerosis in apolipoprotein E knockout (ApoE −/− ) mice. Methods ApoE −/− mice (8-week male) were treated with saline (control), anakinra 10, 25, and 50 mg/kg, respectively (n = 10 in each group). Mice were fed a standard chow (4 weeks) followed by an atherogenic diet (35kcal% fat, 1.25% cholesterol, 12 weeks). Atheromatous plaques and expression of inflammatory genes and signaling pathways in human umbilical vein endothelial cells (HUVECs), rat aortic smooth muscle cells (RAOSMCs), and 3T3-L1 adipocytes were assessed. Results The plaque size of aortic arch (30.6% and 25.2% at the 25mg/kg and 50mg/kg doses, both P < 0.05) and serum triglyceride were significantly reduced in anakinra-treated ApoE −/− mice and inflammatory genes (IL-1β and IL-6) expressions in anakinra-treated HUVECs and RAOSMCs were suppressed (all P < 0.05). In RAOSMCs, anakinra reduced metalloproteinase-9 expression in a dose-dependent manner and inhibited RAOSMC migration in a wound healing assay. Anakinra-treated mice exhibited a trend toward lower CD68 + macrophage infiltration in visceral fat and monocyte chemoattractant protein-1 expression was reduced in 3T3-L1 adipocytes. Conclusion IL-1 blockade with anakinra significantly reduced atherosclerotic plaque formation in ApoE −/− mice. Also, anakinra reduced expression of inflammatory genes in endothelial cells, smooth muscle cells, and adipocytes and ameliorated processes involved in vascular remodeling. Anakinra could be a useful component of complementary treatment with standard regimen to reduce the residual cardiovascular risk." @default.
- W3172989968 created "2021-06-22" @default.
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- W3172989968 date "2021-06-12" @default.
- W3172989968 modified "2023-09-23" @default.
- W3172989968 title "The anti-atherosclerosis effect of anakinra, a recombinant human interleukin-1 receptor antagonist, in apolipoprotein E knockout mice" @default.
- W3172989968 doi "https://doi.org/10.21203/rs.3.rs-482370/v1" @default.
- W3172989968 hasPublicationYear "2021" @default.
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