Print Email Facebook Twitter Hematopoietic α7 nicotinic acetylcholine receptor deficiency increases inflammation and platelet activation status, but does not aggravate atherosclerosis 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 LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy LivingAlpha7 nicotinic acetylcholine receptorAtherosclerosisBone marrow transplantationInflammationPlateletsBungarotoxin receptorC reactive proteinTumor necrosis factor alphaAnimal experimentAnimal modelAtherogenic dietControlled studyDisease courseLeukocyteMesentery lymph nodeMouseNonhumanPeritoneumSpleenThrombocyte activationThrombocyte function To reference this document use: 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 Files To receive the publication files, please send an e-mail request to TNO Library.