In vivo knockdown of nicotinic acetylcholine receptor ?1 diminishes aortic atherosclerosis.

ABSTRACT: Nicotinic acetylcholine receptor ?1 (nAChR?1) was recently identified as a functional cell receptor for urokinase, a potent atherogenic molecule. Here, we test the hypothesis that nAChR?1 plays a role in the pathogenesis of atherosclerosis.Apolipoprotein E-deficient mice were initially fed a Western diet for 8 wks. Plasmid DNA encoding scramble RNA (pscr) or siRNA (psir2) for nAChR?1 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 nAChR?1 gene silencing. The remaining mice continued on a Western diet for an additional 16 wks.The nAChR?1 was up-regulated in aortic atherosclerotic lesions. A 78% knockdown of the nAChR?1 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 nAChR?1 knockdown may involve up-regulating interferon-?/Y box protein-1 activity and down-regulating transforming growth factor-? expression.The nAChR?1 gene plays a significant role at the artery wall, and reducing its expression decreases aortic plaque development.

SUBMITTER: Zhang G 

PROVIDER: S-EPMC3688265 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature