| First Author | Lee RH | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 3 | Pages | e0124584 |
| PubMed ID | 25826262 | Mgi Jnum | J:229565 |
| Mgi Id | MGI:5752446 | Doi | 10.1371/journal.pone.0124584 |
| Citation | Lee RH, et al. (2015) Reduced size and macrophage content of advanced atherosclerotic lesions in mice with bone marrow specific deficiency of alpha 7 nicotinic acetylcholine receptor. PLoS One 10(3):e0124584 |
| abstractText | In macrophages the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) modulates production of inflammatory cytokines, cholesterol accumulation and lipoprotein uptake. Recently, our laboratory showed that selective stimulation of the alpha7nAChR protects macrophages from apoptosis, an effect that is absent in alpha7nAChR-deficient macrophages. All these observations are suggestive of a potential role of macrophage alpha7nAChR in atherosclerosis. Mouse models of the disease with bone marrow deletion of alpha7nAChR represent an attractive approach to address the in vivo relevance of these in vitro findings. However, recent studies that focused on the impact of hematopoietic deficiency of alpha7nAChR on early atherosclerotic lesions of low density lipoprotein receptor knockout (LDLRKO) mice, yielded controversial results. The question also remained whether macrophage alpha7nAChR modulates the characteristics of advanced lesions. Here we used LDLR knockout mice transplanted with bone marrow from wild-type or alpha7nAChR knockout animals to revisit the effect of hematopoietic deficiency of alpha7nAChR on early lesions and to examine, for the first time, its impact on advanced plaques. Aortic sinus atherosclerotic lesions were analyzed following 8 and 14 weeks on a high fat diet. Early lesions in mice with alpha7nAChR deficient bone marrow were not different from those in control animals. However, advanced lesions of mice with bone marrow deletion of alpha7nAChR exhibited reduction in size, macrophage content and cell proliferation. These studies are the first in examining the impact of hematopoietic deficiency of alpha7nAChR on the characteristics of advanced atherosclerotic lesions in a mouse model of the disease and provide novel evidence underscoring a potential pro-atherogenic role of macrophage alpha7nAChR. |
