Atherosclerosis is a chronic inflammatory disease. It has been appreciated that vagus nerve inhibits macrophage activation via α7
nicotinic acetylcholine receptor (nAChR), termed the cholinergic anti-inflammatory pathway. We explored the effects of
AR-R17779, a selective α7nAChR agonist, on
atherosclerosis and
aneurysm formation in
apolipoprotein E (
ApoE)-deficient mice.
ApoE-deficient mice were fed a high-fat diet (HFD) and
angiotensin II (Ang II) was infused by osmotic minipumps from 10-week-old for 4weeks.
AR-R17779 was given in
drinking water ad libitum.
Oil red O staining of the aorta showed that combined loading of HFD and Ang II induced marked
atherosclerosis compared with control mice fed a normal chow. Treatment with
AR-R17779 significantly reduced
atherosclerotic plaque area and improved survival of mice. Treatment with
AR-R17779 also suppressed
abdominal aortic aneurysm formation. Quantitative RT-PCR of the aorta revealed that
mRNA expression levels of interleukin-1β,
interleukin-6 and NOX2 were significantly decreased in AR-R17779-treated mice compared with Ang II+HFD mice.
AR-R17779 treatment also reduced blood pressure and serum
lipid levels. In conclusion, α7nAChR activation attenuates
atherogenesis and aortic abdominal
aneurysm formation in
ApoE-deficient mice possibly through an anti-inflammatory effect and reduction of blood pressure and
lipid levels. Pharmacological activation of α7nAChR may have a therapeutic potential against atherosclerotic
vascular diseases through multiple mechanisms.