Significance of proteoglycan in relation to oxidized low-density lipoprotein and plaque vulnerability

• Project/Area Number: 19591681
• 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: UN0 Masaaki The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 准教授 (90232884)
• 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) ; MATSUBARA Shunji 徳島大学, 医学部・歯学部附属病院, 講師 (60294675) ; NISHI Kyoko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 講師 (60335817)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 頸動脈病変 / CEA / decorin / biglycan / HCII / HC II

Research Abstract

頚動脈脈内膜剥離術の至適な施行時期を解析するため、発症後一週以内の急性期とそれ以後の慢性期に手術により摘出したプラークを免疫組織学的に安定性/不安定性プラークに分類した。さらにプラーク中の酸化LDLおよびマトリックスメタロプロテナーゼ-9(MMP-9)の含有量や活性を測定し、免疫組織学的にこれらの局在を調べた。頚動脈狭窄症例の発症早期に酸化LDL含量やMMP一9の活性が、慢性期に摘出したプラークに較べて上昇していることを明らかにした。さらに酸化LDLのマクロファージへの取り込みに関与するプロテオグリカンであるDecolinやBiglicanの発現量およびその局在を評値し、これらのプロテオグリカンが不安定なプラークに多く発現していることを認めている。またこれらの発現は酸化LDLの増加と相関していた。従来、頚動脈脈内膜剥離術は症状の安定を待って1ヶ月以後に手術が施行されていた。しかし頚動脈狭窄症例では発症早期により強い酸化ストレスや炎症性変化があることを示した本研究結果から、発症早期に手術を行うことが妥当であることを示唆した。この研究から得た知見についてはJournal of Vascular Surgeryに投稿し、受理された

Research Products

• [Journal Article] Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator (2009)
  • Author(s): Yagi K, Kitazato KT, Uno M, Tada Y, Kinouchi T, Shimada K, Nagahiro S
  • Journal Title: Stroke 40 Pages: 626-631
  • Peer Reviewed
• [Journal Article] Endothelial damage due to impaired NO bioavailability triggers cerebral aneurysm formation in female rats-Endothelial damage and cerebral aneurysm (2009)
  • Author(s): Tamura T, Jamous MA, Kitazato KT, Yagi K, Tada Y, Uno M, Nagahiro S.
  • Journal Title: J Hypertens 27(6) Pages: 1284-92
  • Peer Reviewed
• [Journal Article] embolization during carotid angioplasty and carotid artery stenting (2009)
  • Author(s): Yamasaki H, Matsubara S, Sasaki I, Nagahiro S.
  • Journal Title: Neurol Med Chir (Tokyo) 49(5) Pages: 213-6
  • Peer Reviewed
• [Journal Article] Primary anaplastic pleomorphic xanthoastrocytoma with widespread neuroaxis dissemination atdiagnosis--a pediatric case report and review of the literature (2009)
  • Author(s): Okazaki T, Kageji T, Matsuzaki K, Horiguchi H, Hirose T, Watanabe H, Ohnishi T, Nagahiro S.
  • Journal Title: J Neurooncol 27
  • Peer Reviewed
• [Journal Article] Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator (2009)
  • Author(s): Yagi K, Uno M
  • Journal Title: Stroke 40 Pages: 626-631
  • Peer Reviewed
• [Journal Article] Endothelial damage due to impaired NO bioavailability triggers cerebral aneurysm formation in female rats-Endothelial damage and cerebral aneurysm (2009)
  • Author(s): Tamura T, Uno M
  • Journal Title: Journal of Hypertension (印刷中)
  • Peer Reviewed
• [Journal Article] 3-tesla MRI in acute stroke patients (2008)
  • Author(s): Morita N, Harada M, Uno M, Matsubara S, Matsuda T, Nagahiro S, Nishitani H.
  • Journal Title: Cerebrovasc Dis 26(4) Pages: 367-75
• [Journal Article] Protective mechanisms of the angiotensin II type 1 receptor blacker candesartan against cerebral ischemia (2008)
  • Author(s): Liu H, Kitazato KT, Uno M, Yagi K, Kanematsu Y, Tamura T, Tada Y, Kinouchi T, Nagahiro S
  • Journal Title: in-vivo and in-vitro studies, Journal of Hypertension 26(7) Pages: 1435-1445
  • Peer Reviewed
• [Journal Article] Choreoathetosis due to rupture of a distal accessory anterior cerebral artery aneurysm (2008)
  • Author(s): Morigaki R, Uno M, Matsubara S, Satoh K, Nagahiro S.
  • Journal Title: Cerebrovasc Dis 25(3) Pages: 285-7
  • Peer Reviewed
• [Journal Article] Bilateral deep brain stimulation of the glohus pallidus internus in tardive dystonia (2008)
  • Author(s): Sako W, Goto S, Shimazu H, Murase N, Matsuzaki K, Tamura T, Mure H, Tomogane Y, Arita N, Yoshikawa H, Nagahiro S, Kaji R.
  • Journal Title: Mov Disord 23(13) Pages: 1929-31
  • Peer Reviewed
• [Journal Article] Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia (2008)
  • Author(s): Sato K, Sumi-Ichinose C, Kaji R, Ikemoto K, Nomura T, Nagatsu I, Ichinose H, Ito M, Sako W, Nagahiro S, Graybiel AM, Goto S.
  • Journal Title: Proc Natl Acad Sci US A 105(34) Pages: 12551-6
  • Peer Reviewed
• [Journal Article] Protective mechanisms of the angiotensin II type 1 receptor blocker candesartan against cerebral ischemia : in-vivo and in-vitro studies (2008)
  • Author(s): Liu H, Uno M
  • Journal Title: Journal of Hypertension 2 6 Pages: 1435-1445
  • Peer Reviewed
• [Journal Article] Comparison between early and late carotid endarterectomy for symptomatic carotid stenosis in relation to oxidized low-density lipoprotein and plaque vulnerability (2007)
  • Author(s): Suzue A, Uno M, Kitazato KT, Nishi K, Yagi K, Liu H, Tamura T, Nagahiro S.
  • Journal Title: J Vasc Surg 46(5) Pages: 870-5
  • Peer Reviewed
• [Journal Article] Hemodynamic cerebral ischemia during carotid endarterectomy evaluated by intraoperative monitoring and post-operative diffusion-weighted imaging (2007)
  • Author(s): Uno M, Suzue A, Nishi K, Nagahiro S.
  • Journal Title: Neural Res 29(1) Pages: 70-7
  • Peer Reviewed
• [Journal Article] Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation : experimental study in rats (2007)
  • Author(s): Jamous MA, Nagahiro S, Kitazato KT, Tamura T, Aziz HA, Shona M, Satoh K
  • Journal Title: J. Neurosurg 107 Pages: 405-411
  • Peer Reviewed
• [Journal Article] Hemodynamic cerebral ischemia during carotid endarterectomy evaluated by intraoperative monitoring and postoperative diffusion-weigted imaging. (2007)
  • Author(s): Uno M, Suzue A, Nishi K, Nagahiro S
  • Journal Title: Neurol Res 29 Pages: 70-77
  • Peer Reviewed
• [Journal Article] Immunoreactive circulating oxidized HDL concentrations do not increase in patients undergoing carotid endarterectomy:A comparative study for oxidized HDL and oxidized LDL concentrations in plasma (2007)
  • Author(s): Nakano T, Kitazato KT, Uno M, Seo M, Hamaoki M, Komoda T, Nagata A
  • Journal Title: Clin Chim Acta. 381 Pages: 179-181
  • Peer Reviewed
• [Journal Article] Comparison between early and late carotid endarterectomy for symptomatic carotid stenosis in relation to oxidized LDL and plaque vulnerability. (2007)
  • Author(s): Suzue A, Uno M, Kitazato TK, Nishi K, Liu H, Yagi K, Tamura T, Nagahiro S.
  • Journal Title: J Vasc Surg 46 46 Pages: 870-875
  • Peer Reviewed
• [Journal Article] Vascular reconstruction (chronic)- CEA, STA-MCA anastomosis (2006)
  • Author(s): Nishi K, Uno M, Nagahiro S.
  • Journal Title: Nippon Rinsho Nov 28 Pages: 100-3
• [Journal Article] Hemichorea due to hemodynamic ischemia associated with extracranial carotid artery stenosis (2006)
  • Author(s): Morigaki R, Uno M, Suzue A, Nagahiro S.
  • Journal Title: Report of two cases. J Neurosurg 105(1) Pages: 142-7
  • Peer Reviewed
• [Journal Article] Surgical indication and selection of surgical procedure for hypertensive subcortical hemorrhage (2006)
  • Author(s): Toi H, Uno M, Nagahiro S.
  • Journal Title: Nippon Rinsho Nov 28 Pages: 436-41
• [Presentation] a free radical scavenger, inhibits MMP-9 related brain hemorrhage in rats treated with tissue plasminogen activator (2008)
  • Author(s): Uno M, Yagi K, Kitazato KT, Tada Y, Nagahiro S.
  • Organizer: Xth International Symposium on Thromholysis and Acute Stroke Therapy
  • Place of Presentation: Budapest, Hungary
• [Presentation] EDARAVONE, A FREE RADICAL SCAVENGER, INHIBITS MMP-9-RELATED BRAIN HEMORRHAGE IN RATS TREATED WITH TISSUE PLASMINOGEN ACTIVATOR (2008)
  • Author(s): Uno M, Yagi K, Kitazato KT, Tada Y, Kinouchi T, Tamura T, Nagahiro S.
  • Organizer: 6^<th> World Stroke Congress
  • Place of Presentation: Vienna, Austria
• [Presentation] SYSTEMIC- AND FOCAL EFFECTS OF CANDESARTAN AGAINST CEREBRAL ISCHEMIA (2008)
  • Author(s): Kitazato KT, Uno M, Yagi K, Mull, Tamura T, Tada Y, Kinouchi T, Shimada K, Nagahiro S.
  • Organizer: 6^<th> World Stroke Congress
  • Place of Presentation: Vienna, Austria
• [Presentation] Edaravone, a free radical scavenger, inhibits MMP-9 related brain hemorrhage in rats treated with tissue plasminogen activator (2008)
  • Author(s): Uno M
  • Organizer: Xth International Symposium on Throm bolysis and Acute Stroke Therapy
  • Place of Presentation: Budapest, Hungary
• [Remarks]
  • URL: http://www.neurosurgerytokushima.com/