To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Stimulation of alpha 7 ni… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

Stimulation of alpha 7 nicotinic acetylcholine receptor (α7nAChR) inhibits atherosclerosis via immunomodulatory effects on myeloid cells.

Journal article
Authors Marcus A Ulleryd
Filip Mjörnstedt
Dimitra Panagaki
Li Jin Yang
Kajsa Engevall
Saray Gutiérrez
Yixin Wang
Li-Ming Gan
Holger Nilsson
Erik Michaëlsson
Maria E Johansson
Published in Atherosclerosis
Volume 287
Pages 122-133
ISSN 1879-1484
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Physiology
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 122-133
Language en
Links dx.doi.org/10.1016/j.atherosclerosi...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cell biology, Immunology in the medical area, Physiology

Abstract

Alpha 7 nicotinic acetylcholine receptor (α7nAChR) stimulation can regulate acute inflammation, and lack of α7nAChR accelerates atherosclerosis in mice. In this study, we aimed to investigate the effects of the novel α7nAChR agonist, AZ6983, on atherosclerosis and assess its possible immunomodulating effects.AZ6983 was tested in vitro in LPS-challenged mouse and human blood and in vivo using the acute inflammatory air pouch model. Thereafter, long-term effects of AZ6983 treatment on atherosclerosis and immune responses were assessed in apoE-/- mice after 8 and 12 weeks. Atherosclerosis was investigated in the aortic root and thoracic aorta, serum levels of cytokines were analysed and RNAseq was used to study aortic gene expression. Further, bone-marrow-derived macrophages were used to assess phagocytosis in vitro.α7nAChR activation by AZ6983 decreased pro-inflammatory cytokines in acute stimulations of human and mouse blood in vitro, as well as in vivo using the air pouch model. Treating apoE-/- mice with AZ6983 decreased atherosclerosis by 37-49% and decreased serum cytokine levels. RNAseq analysis of aortae suggested the involvement of several specific myeloid cell functions, including phagocytosis. In line with this, AZ6983 significantly increased phagocytosis in bone marrow-derived macrophages.This study demonstrates that activation of α7nAChR with AZ6983 inhibits atherosclerosis in apoE-/-mice and that immunomodulating effects on myeloid cells, such as enhanced phagocytosis and suppression of inflammatory cytokines, could be part of the athero-protective mechanisms. The observed anti-inflammatory effect in human blood supports the idea that AZ6983 may decrease disease also in humans.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?