Suppression of abdominal aortic aneurysm formation by AR-R17779, an agonist for the α7 nicotinic acetylcholine receptor

Aya Watanabe, Toshihiro Ichiki, Hiroshi Kojima, Yusuke Takahara, Eva Hurt-Camejo, Erik Michaëlsson, Chikahiro Sankoda, Jiro Ikeda, Eriko Inoue, Tomotake Tokunou, Shiro Kitamoto, Kenji Sunagawa

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6 Citations (Scopus)

Abstract

Objective: Activation of vagal nerve suppresses inflammatory responses through activation of α7 nicotinic acetylcholine receptor (nAchR). We sought to determine whether AR-R17779, a selective agonist of α7nAchR, affects the development of abdominal aortic aneurysm (AAA). Methods and results: AAA was induced by topical application of calcium chloride (CaCl2) to abdominal aorta (AAA group). NaCl (0.9%) was substituted for CaCl2 as a sham operation (SHAM group). AR-R17779 was administered in drinking water (AAA/AR-R group). One and 6 weeks after the operation, aortic tissue was excised for histological and molecular analyses. Aortic diameter and macrophage infiltration into the aortic adventitia were increased in AAA group compared with SHAM group at 6 weeks. Treatment with AR-R17779 reduced the diameter of the aorta and macrophage infiltration compared with AAA group. Wavy morphology of the elastic lamellae was lost in AAA group while it was preserved in AAA/AR-R group. Expression of inflammatory cytokines and matrix metalloproteinase (MMP) activities were enhanced in AAA group, which was suppressed in AAA/AR-R group. AR-R17779 treatment suppressed CaCl2-induced expression of cytokines, activities of MMPs and NF-κB activation at 1 week when aortic dilatation had not developed. Conclusion: Treatment with AR-R17779 prevented the enlargement of abdominal aorta induced by CaCl2 in association with reduced inflammation and extracellular matrix disruption. These findings suggest therapeutic potential of α7nAchR activation for prevention of AAA development.

Original languageEnglish
Pages (from-to)113-120
Number of pages8
JournalAtherosclerosis
Volume244
DOIs
Publication statusPublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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    Watanabe, A., Ichiki, T., Kojima, H., Takahara, Y., Hurt-Camejo, E., Michaëlsson, E., Sankoda, C., Ikeda, J., Inoue, E., Tokunou, T., Kitamoto, S., & Sunagawa, K. (2016). Suppression of abdominal aortic aneurysm formation by AR-R17779, an agonist for the α7 nicotinic acetylcholine receptor. Atherosclerosis, 244, 113-120. https://doi.org/10.1016/j.atherosclerosis.2015.11.006