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- W2256453104 abstract "Introduction: Innate immunity, particularly monocytes / macrophages and neutrophils, play a major role in the development and the complications of atherosclerosis. TREM-1 is a recently discovered receptor expressed by myeloid cells that amplifies the inflammatory response by increasing chemokines and pro inflammatory cytokines production. The aim of this study was to determine the role of TREM-1 in experimental atherosclerosis. Methods and results: TREM-1 is not present in healthy artery but is expressed (mRNA and protein) in human carotid atherosclerotic plaques, mainly by macrophages. 8 week-old Ldlr-/ - mice were lethally irradiated and transplanted with a bone marrow graft Trem-1 + / + or Trem-1-/ - and put on a fat diet (FD) during 14 weeks. Cholesterol levels were not different between the two groups. In Ldlr-/-/Trem-1-/ - chimeric mice, we observed a 60% reduction of the lesion size in the aortic sinus (120100 ± 139600 vs 479116 ± 70229 μm2, P = 0.006) and a 49% reduction on the thoracic aorta (9.5 ± 2.2 vs 4.8 ± 1.6% surface ratio, P = 0.02). In Ldlr-/-/Trem-1-/- chimeric mice, plaques showed a significant decrease in macrophage infiltration (MOMA +, P=0.029) and a reduction in necrotic core size (Masson’s trichrome, P=0.003). In vitro, splenocytes from Ldlr-/-Trem-1-/- stimulated by oxidized LDL produced less IL-12 (ELISA) than control chimeric splenocytes (126 ±104 vs 1185 ± 795 pg/ml, P = 0.001). We have developed a dodecapeptide (LR-12) wich inhibits TREM-1 binding to its endogenous ligand. Apoe-/- mice were treated by daily intraperitoneal injections of LR-12 (100μg) or scramble peptide during 4 weeks. We observed that LR-12 treatment reduced atherosclerosis development on a chow diet (-30%, P <0.05) and on a high fat diet (-42%, P = 0.005). Conclusion: TREM-1 is expressed in human and mouse atherosclerotic plaques. TREM-1 genetic invalidation and pharmacological inhibition reduce the development of atherosclerosis and induce a more stable plaque phenotype." @default.
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- W2256453104 date "2014-11-25" @default.
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- W2256453104 title "Abstract 18838: Inhibition and Genetic Deficiency of Trem-1 Receptor Reduces Development of Experimental Atherosclerosis in Mice" @default.
- W2256453104 doi "https://doi.org/10.1161/circ.130.suppl_2.18838" @default.
- W2256453104 hasPublicationYear "2014" @default.
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