کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2892884 | 1172397 | 2011 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: In vivo knockdown of nicotinic acetylcholine receptor α1 diminishes aortic atherosclerosis In vivo knockdown of nicotinic acetylcholine receptor α1 diminishes aortic atherosclerosis](/preview/png/2892884.png)
ObjectiveNicotinic acetylcholine receptor α1 (nAChRα1) was recently identified as a functional cell receptor for urokinase, a potent atherogenic molecule. Here, we test the hypothesis that nAChRα1 plays a role in the pathogenesis of atherosclerosis.MethodsApolipoprotein E-deficient mice were initially fed a Western diet for 8 wks. Plasmid DNA encoding scramble RNA (pscr) or siRNA (psir2) for nAChRα1 was injected into the mice (n = 16) using an aortic hydrodynamic gene transfer protocol. Four mice from each group were sacrificed 7 days after the DNA injection to confirm the nAChRα1 gene silencing. The remaining mice continued on a Western diet for an additional 16 wks.ResultsThe nAChRα1 was up-regulated in aortic atherosclerotic lesions. A 78% knockdown of the nAChRα1 gene resulted in remarkably less severe aortic plaque growth and neovascularization at 16 wks (both P < 0.05). In addition, significantly fewer macrophages (60% less) and myofibroblasts (80% less) presented in the atherosclerotic lesion of the psir2-treated mice. The protective mechanisms of the nAChRα1 knockdown may involve up-regulating interferon-γ/Y box protein-1 activity and down-regulating transforming growth factor-β expression.ConclusionsThe nAChRα1 gene plays a significant role at the artery wall, and reducing its expression decreases aortic plaque development.
Journal: Atherosclerosis - Volume 215, Issue 1, March 2011, Pages 34–42