Roles of nicotine in the development of intracranial aneurysm rupture

Yoshinobu Kamio, Takeshi Miyamoto, Tetsuro Kimura, Kazuha Mitsui, Hajime Furukawa, Dingding Zhang, Kimihiko Yokosuka, Masaaki Korai, Daisuke Kudo, Ronald J. Lukas, Michael T. Lawton, Tomoki Hashimoto

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


Background and Purpose: Tobacco cigarette smoking is considered to be a strong risk factor for intracranial aneurysmal rupture. Nicotine is a major biologically active constituent of tobacco products. Nicotine's interactions with vascular cell nicotinic acetylcholine receptors containing α7 subunits (α7*-nAChR) are thought to promote local inflammation and sustained angiogenesis. In this study, using a mouse intracranial aneurysm model, we assessed potential contributions of nicotine exposure and activation of α7*-nAChR to the development of aneurysmal rupture. Methods: Intracranial aneurysms were induced by a combination of deoxycorticosterone-salt induced hypertension and a single-dose elastase injection into cerebrospinal fluid in mice. Results: Exposure to nicotine or an α7*-nAChR-selective agonist significantly increased aneurysm rupture rate. Coexposure to an α7*-nAChR antagonist abolished nicotine's deleterious effect. In addition, nicotine's promotion of aneurysm rupture was absent in smooth muscle cell-specific α7*-nAChR subunit knockout mice but not in mice lacking α7*-nAChR on endothelial cells or macrophages. Nicotine treatment increased the mRNA levels of vascular endothelial growth factor, platelet-derived growth factor-B, and inflammatory cytokines. α7*-nAChR antagonist reversed nicotine-induced upregulation of these growth factors and cytokines. Conclusions: Our findings indicate that nicotine exposure promotes aneurysmal rupture through actions on vascular smooth muscle cell α7*-nAChR.

Original languageEnglish
Pages (from-to)2445-2452
Number of pages8
Issue number10
Publication statusPublished - 2018


  • Animal
  • Intracranial aneurysm
  • Models
  • Nicotine
  • Tobacco
  • α7 nicotinic acetylcholine receptor


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