Bidirectional effects of statins on the formation and growth of cerebral aneurysms

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591844
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: The University of Tokushima
• Principal Investigator: SATOMI Junichiro 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (10304510)
• Co-Investigator(Kenkyū-buntansha): NAGAHIRO Shinji 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (60145315) ; KANEMATSU Yasuhisa 徳島大学, 病院, 助教 (90363142) ; YAGI Kenji 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80551837) ; TADA Yoshiteru 徳島大学, 病院, 助教 (30547964) ; SATA Masataka 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (80345214)
• Project Period (FY): 2009 – 2011
• Keywords: 脳動脈瘤 / 高血圧 / エストロゲン

Research Abstract

Statins exert pleiotropic effects on the vasculature, independent of their cholesterol-lowering properties. In a rat model we studied whether statins prevent the initiation and growth of cerebral aneurysms. A hydrophilic statin at low dose prevented the cerebral aneurysm formation, which was associated with eNOS up-regulation. On the other hand, the statin at high doses and a lipophilic statin promoted aneurysm growth and rupture ; the deleterious effects were associated with vascular apoptosis. Our results issue a warning that statins exert bidirectional effects on cerebral aneurysms.

Research Products

• [Journal Article] Nagahiro S Activation of signal transducer and activator of transcription-3 by a peroxisome proliferator-activated receptor gamma agonist contributes to neuroprotection in the peri-infarct region after ischemia in oophorectomized rats (2012)
  • Author(s): Kinouchi T, Kitazato KT, Shimada K, Yagi K, Tada Y, Matsushita N, Sumiyoshi M, Satomi J, Kageji T
  • Journal Title: Stroke Volume: 43 Pages: 478-83
  • DOI: DOI:10.116.1161/STROKEAHA.111.618926
  • Peer Reviewed
• [Journal Article] Kruppel-like Zinc-Finger Transcription Factor 5(KLF5) Is Highly Expressed in Large and Giant Unruptured Cerebral Aneurysms (2011)
  • Author(s): Nakajima N, Nagahiro S, Sano T, Satomi J, Tada Y, Yagi K, Kitazato KT, Satoh K
  • Journal Title: World Neurosurg Volume: Nov7
  • Peer Reviewed
• [Journal Article] A mouse model of intracranial aneurysm : technical considerations (2011)
  • Author(s): Tada Y, Kanematsu Y, Kanematsu M, Nuki Y, Liang EI, Wada K, Makino H, Hashimoto T
  • Journal Title: Acta Neurochir Suppl Volume: 111 Pages: 31-5
  • DOI: DOI:10.1007/978-3-7091-0693-8_6
  • Peer Reviewed
• [Journal Article] Statins promote the growth of experimentally induced cerebral aneurysms in estrogen-deficient rats (2011)
  • Author(s): Tada Y, Kitazato KT, Yagi K, Shimada K, Matsushita N, Kinouchi T, Kanematsu Y, Satomi J, Kageji T, Nagahiro S
  • Journal Title: Stroke Volume: 42 Pages: 2286-93
  • DOI: DOI:10.1161/STROKEAHA.110.608034
  • Peer Reviewed
• [Journal Article] Activation of estrogen receptor-αand of angiotensin-converting enzyme 2 suppresses ischemic brain damage in oophorectomized rats (2011)
  • Author(s): Shimada K, Kitazato KT, Kinouchi T, Yagi K, Tada Y, Satomi J, Kageji T, Nagahiro S
  • Journal Title: Hypertension Volume: 57 Pages: 1161-6
  • DOI: DOI:10.1161/HYPERTENSIONAHA.110.167650
  • Peer Reviewed
• [Journal Article] Reduction of endothelial tight junction proteins is related to cerebral aneurysm formation in rats (2010)
  • Author(s): Tada Y, Yagi K, Kitazato KT, Tamura T, Kinouchi T, Shimada K, Matsushita N, Nakajima N, Satomi J, Kageji T, Nagahiro S
  • Journal Title: J Hypertens Volume: 28 Pages: 1883-91
  • DOI: DOI:10.116/HYPERTENSIONAHA.109.134130
  • Peer Reviewed
• [Journal Article] Incidence and clinical correlation of intracranial hemorrhages observed by 3-tesla gradient echo T(2)*-weighted images following intravenous thrombolysis with recombinant tissue plasminogen activator (2010)
  • Author(s): Harada M, Morita N, Uno M, Satomi J, Izumi Y, Asanuma K, Nishitani H, Kaji R, Nagahiro S
  • Journal Title: Cerebrovasc Dis Volume: 29 Pages: 571-5
  • Peer Reviewed
• [Journal Article] Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats (2010)
  • Author(s): Yagi K, Tada Y, Kitazato KT, Tamura T, Satomi J, Nagahiro S
  • Journal Title: Neurosurgery Volume: 66 Pages: 551-9
  • DOI: DOI:10.1227/01.NEU.0000365771.89576.77
  • Peer Reviewed
• [Journal Article] Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats (2009)
  • Author(s): Tada Y, Kitazato KT, Tamura T, Yagi K, Shimada K, Kinouchi T, Satomi J, Nagahiro S
  • Journal Title: Hypertension Volume: 54 Pages: 552-7
  • DOI: DOI:10.116/HYPERTENSIONAHA.109.134130
• [Journal Article] Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats (2009)
  • Author(s): Tamura T, Jamous MA, Kitazato KT, Yagi K, Tada Y, Uno M, Nagahiro S
  • Journal Title: J Hypertens Volume: 27 Pages: 1284-92
  • DOI: DOI:10.1097/HJH.0b013e328329d1a7
  • Peer Reviewed
• [Presentation] ACTIVATION OF NUCLEAR RECEPTORS ON NEUROPROTECTION AFTER EXPERIMENTAL CEREBRAL ISCHEMIA IN FEMALE RATS (2012)
  • Author(s): Kohrai M, Kitazato KT., Kinouchi T, Shimada K, Sumiyoshi M, Matsushita N, Kanematsu Y, Satomi J, Kageji T, Nagahiro S
  • Organizer: 80^<th> AANS
  • Place of Presentation: Miami, Florida
  • Year and Date: 20120414-18
• [Presentation] Excessive salt-intake exacerbates ischemic brain damage independent of blood pressure (2012)
  • Author(s): Sumiyoshi M, Kinouchi T, Tsutsumi T, Kitazato K, Shimada K, Matsushita N, Kanematsu Y, Satomi J, Nagahiro S
  • Organizer: 80^<th> AANS
  • Place of Presentation: Miami, Florida
  • Year and Date: 20120414-18
• [Presentation] Nagahiro S Influence of sodium retention on the formation of cerebral aneurysm (2012)
  • Author(s): Matsushita N, Kitazato K, Shimada K, Kinouchi T, Kanematsu Y, Satomi J
  • Organizer: 80^<th> AANS
  • Place of Presentation: Miami, Florida
  • Year and Date: 20120414-18
• [Presentation] High salt-intake under hypoestrogenicity exacerbates ischemic brain damage (2011)
  • Author(s): Sumiyoshi M, Kitazato KT, Kinouchi T, Tsutsumi T, Shimada K, Matsushita N, Kanematsu Y., Satomi J., Nagahiro S
  • Organizer: without affecting the blood pressure Brain & Pet
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20110525-28