期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 13, 期 1, 页码 126-135出版社
WILEY
DOI: 10.1111/jth.12765
关键词
alpha7 nicotinic acetylcholine receptor; atherosclerosis; bone marrow transplantation; inflammation; platelets
资金
- Netherlands Cardio-Vascular Research Initiative: the Dutch Heart Foundation
- Dutch Federation of University Medical Centers
- Netherlands Organisation for Health Research and Development
- Royal Netherlands Academy of Sciences for the GENIUS project 'Generating the best evidence-based pharmaceutical targets for atherosclerosis' [CVON2011-19]
- Netherlands Heart Foundation [2009T038]
- Landsteiner Foundation for Blood Transfusion Research [0912F]
BackgroundThe autonomic nervous system attenuates inflammation through activation of the 7 nicotinic acetylcholine receptor (7nAChR), a pathway termed the cholinergic anti-inflammatory reflex. Interestingly, 7nAChR is expressed on immune cells and platelets, both of which play a crucial role in the development of atherosclerosis. ObjectiveTo investigate the role of hematopoietic 7nAChR in inflammation and platelet function in atherosclerotic ldlr(-/-) mice and to identify its consequences for atherosclerotic lesion development. MethodsBone marrow from 7nAChR(-/-) mice or wild-type littermates was transplanted into irradiated ldlr(-/-) mice. After a recovery period of 8weeks, the mice were fed an atherogenic Western-type diet for 7weeks. ResultsHematopoietic 7nAChR 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 (TNF, 1.6-fold, P<0.01; CRP, 1.8-fold, P<0.01) as well as in the spleen (TNF, 1.6-fold, P<0.01). The lack of 7nAChR on platelets from these mice increased the expression of active integrin (IIb3) upon stimulation by ADP (1.9-fold, P<0.01), indicating increased activation status, while incubation of human platelets with an 7nAChR agonist decreased aggregation (-35%, P<0.05). Despite the large effects of hematopoietic 7nAChR deficiency on inflammatory status and platelet function, it did not affect atherosclerosis development or composition of lesions. ConclusionsHematopoietic 7nAChR is important for attenuation of inflammatory responses and maintaining normal platelet reactivity, but loss of hematopoietic 7nAChR does not aggravate development of atherosclerosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据