title: α7 Nicotinic acetylcholine receptor is expressed in human atherosclerosis and inhibits disease in mice--brief report.
abstract: OBJECTIVE
  Cholinergic pathways of the autonomic nervous system are known to modulate inflammation. Because atherosclerosis is a chronic inflammatory condition, we tested whether cholinergic signaling operates in this disease. We have analyzed the expression of the α7 nicotinic acetylcholine receptor (α7nAChR) in human atherosclerotic plaques and studied its effects on the development of atherosclerosis in the hypercholesterolemic Ldlr(-/-) mouse model.
  
  
  RESULTS
  α7nAChR protein was detected on T cells and macrophages in surgical specimens of human atherosclerotic plaques. To study the role of α7nAChR signaling in atherosclerosis, male Ldlr(-/-) mice were lethally irradiated and reconstituted with bone marrow from wild-type or α7nAChR-deficient animals. Ablation of hematopoietic cell α7nAChR increased aortic atherosclerosis by 72%. This was accompanied by increased aortic interferon-γ mRNA, implying increased Th1 activity in the absence of α7nAChR signaling.
  
  
  CONCLUSIONS
  The present study shows that signaling through hematopoietic α7nAChR inhibits atherosclerosis and suggests that it operates by modulating immune inflammation. Given the observation that α7nAChR is expressed by T cells and macrophages in human plaques, our findings support the notion that cholinergic regulation may act to inhibit disease development also in man.
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. maria.e.johansson@neuro.gu.se.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Ulleryd
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Angelina
authors.initials: A
authors.lastname: Bernardi
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lundberg
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Annica
authors.initials: A
authors.lastname: Andersson
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Fogelstrand
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Zhong-Qun
authors.initials: ZQ
authors.lastname: Yan
authors.affiliation: From the Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (M.E.J., A.M.L., L.Folkersen, Z.-q.Y., G.K.H.); and Department of Physiology, Institute of Neuroscience and Physiology (M.E.J., M.A.U.), Department of Rheumatology and Inflammation Research, Institute of Medicine (A.B., A.A., U.I.), and Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine (L.Fogelstrand), The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D016893:Carotid Stenosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D018183:Transplantation Chimera; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011973:Receptors, LDL; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: alpha7 nicotinic acetylcholine receptor; atherosclerosis; inflammation