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

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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

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Aortic Aneurysm
Nicotinic Receptors
Apolipoproteins E
Atherosclerosis
High Fat Diet
Angiotensin II
Abdominal Aortic Aneurysm
Aorta
Anti-Inflammatory Agents
Blood Pressure
Lipids
Vagus Nerve
Macrophage Activation
Atherosclerotic Plaques
AR-R 17779
Interleukin-1
Vascular Diseases
Drinking Water
Cholinergic Agents
Aneurysm

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

Stimulation of α7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice. / Hashimoto, Toru; Ichiki, Toshihiro; Watanabe, Aya; Hurt-Camejo, Eva; Michaëlsson, Erik; Ikeda, Jiro; Inoue, Eriko; Matsuura, Hirohide; Tokunou, Tomotake; Kitamoto, Shiro; Sunagawa, Kenji.

In: Vascular Pharmacology, Vol. 61, No. 2-3, 05.2014, p. 49-55.

Research output: Contribution to journalArticle

Hashimoto, Toru ; Ichiki, Toshihiro ; Watanabe, Aya ; Hurt-Camejo, Eva ; Michaëlsson, Erik ; Ikeda, Jiro ; Inoue, Eriko ; Matsuura, Hirohide ; Tokunou, Tomotake ; Kitamoto, Shiro ; Sunagawa, Kenji. / Stimulation of α7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice. In: Vascular Pharmacology. 2014 ; Vol. 61, No. 2-3. pp. 49-55.
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