alpha 7 Nicotinic Acetylcholine Receptor Is Expressed in Human Atherosclerosis and Inhibits Disease in Mice-Brief Report
Objective-Cholinergic pathways of the autonomic nervous system are known to modulate inflammation. Because atherosclerosis is a chronic inflammatory condition, we tested whether cholinergic signaling operates in this disease. We have analyzed the expression of the alpha 7 nicotinic acetylcholine rec...
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Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2014, Vol.34 (12), p.2632 |
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Sprache: | eng |
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Zusammenfassung: | Objective-Cholinergic pathways of the autonomic nervous system are known to modulate inflammation. Because atherosclerosis is a chronic inflammatory condition, we tested whether cholinergic signaling operates in this disease. We have analyzed the expression of the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) in human atherosclerotic plaques and studied its effects on the development of atherosclerosis in the hypercholesterolemic Ldlr(-/-) mouse model. Approach and Results-alpha 7nAChR protein was detected on T cells and macrophages in surgical specimens of human atherosclerotic plaques. To study the role of alpha 7nAChR signaling in atherosclerosis, male Ldlr(-/-) mice were lethally irradiated and reconstituted with bone marrow from wild-type or alpha 7nAChR-deficient animals. Ablation of hematopoietic cell alpha 7nAChR increased aortic atherosclerosis by 72%. This was accompanied by increased aortic interferon-gamma mRNA, implying increased Th1 activity in the absence of a7nAChR signaling. Conclusions-The present study shows that signaling through hematopoietic alpha 7nAChR inhibits atherosclerosis and suggests that it operates by modulating immune inflammation. Given the observation that alpha 7nAChR is expressed by T cells and macrophages in human plaques, our findings support the notion that cholinergic regulation may act to inhibit disease development also in man. |
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ISSN: | 1079-5642 |
DOI: | 10.1161/atvbaha.114.303892 |