BS39 TRIB3 deficiency increases plaque stability by altering macrophage function

Laura Martinez Campesino; Jessica M Johnston; Sheila E Francis; Endre Kiss-Toth; Heather L Wilson. Department of Infection, Immunity & Cardiovascular Disease, Medical School, Beech Hill Road, University of Sheffield, UK. Background Metabolic dysfunction and chronic inflammation under obesity are key factors promoting atherosclerosis. Macrophages are the major immune cell type found in atherosclerotic lesions, where plaque macrophages engulf oxidised lipids forming foam cells and also regulate plaque stability. Tribbles (Trib) 3 is a pseudokinase known to be involved in the regulation of adipose homeostasis, lipid and glucose metabolism and macrophage lipid uptake. We propose that Trib3 has a role in regulating metabolic and immune responses to obesity ultimately affecting atherosclerosis development. Methodology. Trib3KO and Trib3WT mice were injected with rAAV8/mPCSK9 and fed with western diet for 12 weeks to promote atherosclerosis development. Atherosclerotic plaques were quantified using Oil-red-O and aortic root lesions were characterised histologically. Primary macrophages from bone marrow (BMDMs) were isolated from these strains and human monocyte derived macrophages (MDMs) were used to further characterise the effects of Trib3 regulating macrophage function. Results En face analysis of the aortae showed no statistical differences in atheroma burden, while histological examination of the plaques indicated an increase in plaque stability in the absence of Trib3. Trib3KO BMDMs showed differential expression of genes involved in macrophage metabolism and regulation of the cytoskeleton. The differential expression of these genes was assessed in human MDMs following control or siTRIB3 treatment. Conclusion These results suggest a role for Trib3 in the regulation of macrophage function promoting plaque stability, and may also have an impact on atherosclerosis development. Conflict of interest No COI