| First Author | Wilund KR | Year | 2009 |
| Journal | Biochem Biophys Res Commun | Volume | 390 |
| Issue | 1 | Pages | 148-54 |
| PubMed ID | 19785985 | Mgi Jnum | J:155229 |
| Mgi Id | MGI:4413375 | Doi | 10.1016/j.bbrc.2009.09.088 |
| Citation | Wilund KR, et al. (2009) Macrophages from alpha 7 nicotinic acetylcholine receptor knockout mice demonstrate increased cholesterol accumulation and decreased cellular paraoxonase expression: a possible link between the nervous system and atherosclerosis development. Biochem Biophys Res Commun 390(1):148-54 |
| abstractText | OBJECTIVE: The parasympathetic nervous system regulates inflammation in peripheral tissues through a pathway termed the 'cholinergic anti-inflammatory reflex' (CAIR). Mice deficient in the alpha 7 nicotinic acetylcholine receptor (alpha7(-/-)) have an impaired CAIR due to decreased signaling through this pathway. The purpose of this study was to determine if the increased inflammation in alpha7(-/-) mice is associated with enhanced serum and macrophage atherogenicity. METHODS: We measured serum markers of inflammation and oxidative stress, and macrophage atherogenicity in mouse peritoneal macrophages harvested from alpha7(-/-) mice on the background of C57BL/6 mice, as well as on the background of the atherosclerotic Apolipoprotein E-deficient (ApoE(-/-)) mice. RESULTS: alpha7-Deficiency had no significant effects on serum cholesterol, or on markers of serum oxidative stress (TBARS and paraoxonase1 activities). However, alpha7-deficiency significantly increased serum CRP and IL-6 (p<0.05) levels in atherosclerotic mice, confirming an anti-inflammatory role for the alpha7 receptor. Macrophage cholesterol mass was increased by 25% in both normal and atherosclerotic mice in the absence of the alpha7 receptor (p<0.05). This was accompanied by conditional increases in oxidized LDL uptake and in macrophage total peroxide levels. Furthermore, alpha7-deficiency reduced macrophage paraoxonase2 mRNA and activity by 50-100% in normal and atherosclerotic mice (p<0.05 for each), indicating a reduction in macrophage anti-oxidant capacity in the alpha7(-/-) mice. CONCLUSION: The above results suggest an anti-atherogenic role for the macrophage alpha7nAchr, through a mechanism that involves attenuated macrophage oxidative stress and decreased uptake of oxidized LDL. |
