Stimulation of α7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice

Toru Hashimoto, Toshihiro Ichiki, Aya Watanabe, Eva Hurt-Camejo, Erik Michaëlsson, Jiro Ikeda, Eriko Inoue, Hirohide Matsuura, Tomotake Tokunou, Shiro Kitamoto, Kenji Sunagawa

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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 4. weeks. 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.

Original languageEnglish
Pages (from-to)49-55
Number of pages7
JournalVascular Pharmacology
Volume61
Issue number2-3
DOIs
Publication statusPublished - May 2014

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Stimulation of α7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice'. Together they form a unique fingerprint.

Cite this