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Cholinergic signaling through the alpha 7 nicotinic receptor inhibits atherosclerosis in hypercholesterolemic mice (671.7)
Author(s) -
Ulleryd Marcus,
Johansson Maria,
Lundberg Anna,
Folkersen Lasse,
Fogelstrand Linda,
Yan ZhongQun,
Hansson Göran
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.671.7
Subject(s) - cholinergic , bone marrow , inflammation , ldl receptor , receptor , immune system , nicotinic acetylcholine receptor , medicine , haematopoiesis , nicotinic agonist , endocrinology , biology , immunology , cholesterol , microbiology and biotechnology , lipoprotein , stem cell
Objective: The aim was to examine the expression of the alpha 7 nicotinic acetylcholine receptor (α7R) in human atherosclerotic plaques and to investigate α7R effects on progression of atherosclerosis in hypercholesterolemic Ldlr‐/‐ mice. Methods: Human carotid plaques and aortic lesions of hypercholesterolemic mice were stained for α7R, using immunohistochemistry. To study the role of cholinergic signaling in atherosclerosis, male Ldlr‐/‐ mice were lethally irradiated and reconstituted with bone marrow from wildtype (WT) or α7R deficient animals. Results: α7R was detected on T cells and macrophages in human carotid plaques. Ablation of hematopoietic cell α7R in Ldlr‐/‐ mice increased aortic atherosclerosis by 38%. This was accompanied by increased aortic interferon‐γ mRNA, implying increased Th1 activity in the absence of α7R signaling. Conclusion: α7R is expressed by T cells and macrophages in human plaques. Lack of α7R in bone marrow dramatically accelerates atherosclerosis in LDLr‐/‐ mice. The present study suggests that cholinergic signaling through hematopoietic α7R inhibits atherosclerosis by modulating immune inflammation.