| First Author | Kooijman S | Year | 2015 |
| Journal | J Thromb Haemost | Volume | 13 |
| Issue | 1 | Pages | 126-35 |
| PubMed ID | 25345495 | Mgi Jnum | J:328396 |
| Mgi Id | MGI:6880287 | Doi | 10.1111/jth.12765 |
| Citation | Kooijman S, et al. (2015) Hematopoietic alpha7 nicotinic acetylcholine receptor deficiency increases inflammation and platelet activation status, but does not aggravate atherosclerosis. J Thromb Haemost 13(1):126-35 |
| abstractText | BACKGROUND: The autonomic nervous system attenuates inflammation through activation of the alpha7 nicotinic acetylcholine receptor (alpha7nAChR), a pathway termed the cholinergic anti-inflammatory reflex. Interestingly, alpha7nAChR 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 alpha7nAChR in inflammation and platelet function in atherosclerotic ldlr(-/-) mice and to identify its consequences for atherosclerotic lesion development. METHODS: Bone marrow from alpha7nAChR(-/-) 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 alpha7nAChR 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 (TNFalpha, 1.6-fold, P < 0.01; CRP, 1.8-fold, P < 0.01) as well as in the spleen (TNFalpha, 1.6-fold, P < 0.01). The lack of alpha7nAChR on platelets from these mice increased the expression of active integrin alphaIIb beta3 upon stimulation by ADP (1.9-fold, P < 0.01), indicating increased activation status, while incubation of human platelets with an alpha7nAChR agonist decreased aggregation (-35%, P < 0.05). Despite the large effects of hematopoietic alpha7nAChR deficiency on inflammatory status and platelet function, it did not affect atherosclerosis development or composition of lesions. CONCLUSIONS: Hematopoietic alpha7nAChR is important for attenuation of inflammatory responses and maintaining normal platelet reactivity, but loss of hematopoietic alpha7nAChR does not aggravate development of atherosclerosis. |
