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

• Project/Area Number: 25860134
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Fukuoka 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: ¥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.

Research Products

• [Journal Article] Varenicline aggravates plaque formation through α7 nicotinic acetylcholine (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 Pages: 194-197
  • DOI: 10.1016/j.bbrc.2014.10.150.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] BMP4 is increased in the aortas of diabetic ApoE knockout mice and enhances 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 Pages: -
  • DOI: 10.1186/1476-9255-10-32.
  • 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 Pages: H747-H755
  • DOI: 10.1152/ajpheart.00825.2012.
  • 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
• [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
  • Year and Date: 20140319-20140321
• [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 – 2014-11-23