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Varenicline aggravates plaque formation through alpha7 nicotinic acetylcholine receptors in ApoE KO mice.

Research Project

Project/Area Number 25860134
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionFukuoka University

Principal Investigator

KOGA Mitsuhisa  福岡大学, 薬学部, 助教 (60570801)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords副作用 / 心血管イベント / バレニクリン
Outline of Final Research Achievements

Smoking is an important causative and/or risk factor for the induction and development of cardiovascular disease. Varenicline is one of the most widely used drugs for smoking cessation. However, whether increased risk of serious cardiovascular events is an adverse effect of varenicline remains controversial. In this study, we determined if varenicline increases the risk of cardiovascular events using apolipoprotein E knockout (ApoE KO) mice. ApoE KO mice (8 weeks old) were injected with varenicline 0.5 mg kg-1 day-1 for 3 weeks. Varenicline aggravated atherosclerotic plaque formation in whole aorta from ApoE KO mice compared with vehicle. Methyllycaconitine, an α7 nicotinic acetylcholine receptor (nAChR) antagonist, inhibited varenicline-induced aggravated plaque formation. Our findings show that varenicline progresses atherosclerotic plaque formation through α7 nAChR, and thereby increases the risk of cardiovascular events.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2015 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Varenicline aggravates plaque formation through α7 nicotinic acetylcholine receptors in ApoE KO mice.2014

    • Author(s)
      Koga M, Kanaoka Y, Ohkido Y, Kubo N, Ohishi K, Sugiyama K, Yamauchi A, Kataoka Y
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 455(3-4) Issue: 3-4 Pages: 194-7

    • DOI

      10.1016/j.bbrc.2014.10.150

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BMP4 is increased in the aortas of diabetic ApoE knockout mice andenhances uptake of oxidized low density lipoprotein into peritoneal macrophages.2013

    • Author(s)
      Koga M, Yamauchi A, Kanaoka Y, Jige R, Tsukamoto A, Teshima N, Nishioku T,Kataoka Y.
    • Journal Title

      J Inflamm

      Volume: 10(1) Issue: 1 Pages: 32-32

    • DOI

      10.1186/1476-9255-10-32

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db/db mice.2013

    • Author(s)
      Koga M, Engberding N, Dikalova AE, Chang KH, Seidel-Rogol B, Long JS, Lassègue B, Jo H, Griendling KK.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 305 Issue: 5 Pages: H747-H755

    • DOI

      10.1152/ajpheart.00825.2012

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] バレニクリンによるα7nAChRを介する動脈硬化巣形成の増悪作用2015

    • Author(s)
      金岡祐輝、古賀允久、大石かおる、杉山慶太、江島優佳、久永真未、山内淳史、片岡泰文
    • Organizer
      第135回薬学会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 禁煙補助薬バレニクリンによる心血管系有害事象2014

    • Author(s)
      金岡祐輝、古賀允久、大石かおる、杉山慶太、江島優佳、久永真美、山内淳史、片岡泰文
    • Organizer
      第67回日本薬理学会西南部会
    • Place of Presentation
      北九州:産業医科大学
    • Year and Date
      2014-11-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] BMP4は、CD36発現を増加させることによりマクロファージの酸化LDL取り込みを促進させる。2014

    • Author(s)
      Kanaoka Y, Koga M, Kubo N, Ohkido Y, Sugiyama K, Ohishi K, Yamauchi A, Kataoka Y
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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