Abstract
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.
Original language | English (US) |
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Pages (from-to) | 34-42 |
Number of pages | 9 |
Journal | Atherosclerosis |
Volume | 215 |
Issue number | 1 |
DOIs | |
State | Published - Mar 2011 |
Keywords
- Atherosclerosis
- Gene knockdown
- Interferon-γ
- Nicotinic acetylcholine receptor α1
- Transforming growth factor-γ
- Y-box protein-1
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine