Title
Hematopoietic α7 nicotinic acetylcholine receptor deficiency increases inflammation and platelet activation status, but does not aggravate atherosclerosis
Author
Kooijman, S.
Meurs, I.
van der Stoep, M.
Habets, K.L.
Lammers, B.
Berbée, J.F.P.
Havekes, L.M.
van Eck, M.
Romijn, J.A.
Korporaal, S.J.A.
Rensen, P.C.N.
Publication year
2015
Abstract
Summary: Background: The autonomic nervous system attenuates inflammation through activation of the α7 nicotinic acetylcholine receptor (α7nAChR), a pathway termed the cholinergic anti-inflammatory reflex. Interestingly, α7nAChR is expressed on immune cells and platelets, both of which play a crucial role in the development of atherosclerosis. Objective: To investigate the role of hematopoietic α7nAChR in inflammation and platelet function in atherosclerotic ldlr-/- mice and to identify its consequences for atherosclerotic lesion development. Methods: Bone marrow from α7nAChR-/- mice or wild-type littermates was transplanted into irradiated ldlr-/- mice. After a recovery period of 8 weeks, the mice were fed an atherogenic Western-type diet for 7 weeks. Results: Hematopoietic α7nAChR deficiency clearly increased the number of leukocytes in the peritoneum (2.6-fold, P < 0.001), blood (2.9-fold; P < 0.01), mesenteric lymph nodes (2.0-fold; P < 0.001) and spleen (2.2-fold; P < 0.01), indicative of an increased inflammatory status. Additionally, expression of inflammatory mediators was increased in peritoneal leukocytes (TNFα, 1.6-fold, P < 0.01; CRP, 1.8-fold, P < 0.01) as well as in the spleen (TNFα, 1.6-fold, P < 0.01). The lack of α7nAChR on platelets from these mice increased the expression of active integrin αIIbβ3 upon stimulation by ADP (1.9-fold, P < 0.01), indicating increased activation status, while incubation of human platelets with an α7nAChR agonist decreased aggregation (-35%, P < 0.05). Despite the large effects of hematopoietic α7nAChR deficiency on inflammatory status and platelet function, it did not affect atherosclerosis development or composition of lesions. Conclusions: Hematopoietic α7nAChR is important for attenuation of inflammatory responses and maintaining normal platelet reactivity, but loss of hematopoietic α7nAChR does not aggravate development of atherosclerosis.
Subject
Life
MHR - Metabolic Health Research
ELSS - Earth, Life and Social Sciences
Biomedical Innovation
Biology
Healthy Living
Alpha7 nicotinic acetylcholine receptor
Atherosclerosis
Bone marrow transplantation
Inflammation
Platelets
Bungarotoxin receptor
C reactive protein
Tumor necrosis factor alpha
Animal experiment
Animal model
Atherogenic diet
Controlled study
Disease course
Leukocyte
Mesentery lymph node
Mouse
Nonhuman
Peritoneum
Spleen
Thrombocyte activation
Thrombocyte function
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http://resolver.tudelft.nl/uuid:a5047fbc-776b-49d0-81ed-77d40a937f66
DOI
https://doi.org/10.1111/jth.12765
TNO identifier
522519
ISSN
1538-7933
Source
Journal of Thrombosis and Haemostasis, 13 (1), 126-135
Document type
article