Treating ApoE−/− mice with Toll-like receptor 7 ligand lead to expansion of marginal zone B cells, reduced plasma cholesterol and decreased atherosclerosis. (25th November 2020)

• Record Type: Journal Article
• Authors: Paulsson-Berne, G; Karadimou, G; Gistera, A; Gallina, A; Centa, M; Salagianni, M; Andreakos, E; Hansson, G.K; Malin, S; Olofsson, P
• Is Part Of: European heart journal. Volume 41:(2020)Supplement 2
• Publication Date: 2020-11-25
• Subjects: Basic Science - Vascular Diseases: Leukocytes, Inflammation, Immunity; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/ehjci/ehaa946.3832
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Background: The interplay between innate and adaptive immunity is involved in the cause of the life-threatening events in atherosclerosis, such as myocardial infarction and stroke. We have previously shown that higher levels of Toll-like receptor 7 (TLR7) expression in human atherosclerotic lesions are correlated to better patient outcome, emphasizing the role of the innate pattern recognizing receptors in the pathogenesis of atherosclerosis. Purpose: Firstly, to investigate if activation of the innate immune receptor TLR7 in vivo in experimental atherosclerosis is a potential way to reduce disease and secondly to identify pathways upon TLR7 ligation treatment. Methods: Apolipoprotein E (ApoE−/−) deficient mice with established disease were injected intraperitoneal with a TLR7 ligand. Local effects were evaluated by characterization of atherosclerotic lesions. Systemic effects of the treatment were investigated by immune composition analysis in the spleen and by plasma measurements Results: In vivo treatment of ApoE−/−mice with TLR7 ligand arrested atherosclerotic lesion development in the aortic root. Moreover, in the lesions of the treated mice we detected decrease in necrotic area and decrease in accumulation of apoptotic cells. In the spleen we detected an expansion of marginal zone B cells accompanied with an increase in IgM antibodies against oxidized low-density lipoprotein (oxLDL). The treated mice had reduced plasma cholesterol levels. Conclusions: In vivo administration of TLR7 ligand ameliorated the atherosclerotic burden in old ApoE−/− mice. Our findings indicate that TLR7 ligation is involved in control of inflammatory responses in atherosclerosis, suggesting that TLR7 is a potential therapeutic target. Further analysis is needed in order to elucidate the underlying mechanisms by which TLR7 exerts its protective role. Funding Acknowledgement: Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Swedish Heart-Lung Foundation