OBJECTIVE: Nicotinic 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. METHODS: Apolipoprotein 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. RESULTS: The 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. CONCLUSIONS: The nAChRα1 gene plays a significant role at the artery wall, and reducing its expression decreases aortic plaque development. Published by Elsevier Ireland Ltd.
OBJECTIVE:Nicotinic 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. METHODS:Apolipoprotein 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. RESULTS: The 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. CONCLUSIONS: The nAChRα1 gene plays a significant role at the artery wall, and reducing its expression decreases aortic plaque development. Published by Elsevier Ireland Ltd.
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Authors: Guoqiang Zhang; Heungsoo Kim; Xiaohe Cai; Jesus M Lopez-Guisa; Peter Carmeliet; Allison A Eddy Journal: J Am Soc Nephrol Date: 2003-05 Impact factor: 10.121
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Authors: Megan S Inkeles; Rosane Mb Teles; Delila Pouldar; Priscila R Andrade; Cressida A Madigan; David Lopez; Mike Ambrose; Mahdad Noursadeghi; Euzenir N Sarno; Thomas H Rea; Maria T Ochoa; M Luisa Iruela-Arispe; William R Swindell; Tom Hm Ottenhoff; Annemieke Geluk; Barry R Bloom; Matteo Pellegrini; Robert L Modlin Journal: JCI Insight Date: 2016-09-22
Authors: Kyle M Walsh; Christopher I Amos; Angela S Wenzlaff; Ivan P Gorlov; Jennette D Sison; Xifeng Wu; Margaret R Spitz; Helen M Hansen; Emily Y Lu; Chongjuan Wei; Huifeng Zhang; Wei Chen; Stacy M Lloyd; Marsha L Frazier; Paige M Bracci; Michael F Seldin; Margaret R Wrensch; Ann G Schwartz; John K Wiencke Journal: Oncotarget Date: 2012-11