title: Varenicline aggravates plaque formation through α7 nicotinic acetylcholine receptors in ApoE KO mice.
abstract: Varenicline is one of the most widely used drugs for smoking cessation. However, whether an adverse effect of varenicline is associated with the risk of serious cardiovascular events 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.
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kanaoka
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Ohkido
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Naoka
authors.initials: N
authors.lastname: Kubo
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ohishi
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. Electronic address: ykataoka@fukuoka-u.ac.jp.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001552:Benzazepines / Q000009:adverse effects* / Q000737:chemistry; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018722:Nicotinic Agonists / Q000009:adverse effects* / Q000737:chemistry; D058226:Plaque, Atherosclerotic / Q000139:chemically induced* / Q000235:genetics; D011810:Quinoxalines / Q000009:adverse effects* / Q000737:chemistry; D000068580:Varenicline; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D002784:Cholesterol; D000068580:Varenicline; D000157:Aconitine
keywords: Adverse cardiovascular effect; Atherosclerosis; Varenicline; α7 nAChR