In vivo knockdown of nicotinic acetylcholine receptor α1 diminishes aortic atherosclerosis

Guoqiang Zhang, Amanda L. Marshall, Alison L. Thomas, Kelly A. Kernan, Yanyuan Su, Renee C. LeBoeuf, Xiu Rong Dong, B. N Angela Tchao

Research output: Contribution to journalArticle

16 Scopus citations

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 languageEnglish (US)
Pages (from-to)34-42
Number of pages9
JournalAtherosclerosis
Volume215
Issue number1
DOIs
StatePublished - 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

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    Zhang, G., Marshall, A. L., Thomas, A. L., Kernan, K. A., Su, Y., LeBoeuf, R. C., Dong, X. R., & Tchao, B. N. A. (2011). In vivo knockdown of nicotinic acetylcholine receptor α1 diminishes aortic atherosclerosis. Atherosclerosis, 215(1), 34-42. https://doi.org/10.1016/j.atherosclerosis.2010.07.057