calcified carotid plaque and inflammation/calcification-related genes

• Project/Area Number: 23592102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Nagoya City University
• Principal Investigator: KATANO Hiroyuki 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (30295612)
• Co-Investigator(Kenkyū-buntansha): YAMADA Kazuo 名古屋市立大学, 大学院医学研究科, 教授 (90150341)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 頚動脈狭窄症 / 頚動脈プラーク / 石灰化 / 網羅的遺伝子発現 / マイクロアレイ / ANGPTL4 / FGFR2 / 頸動脈狭窄症 / 頸動脈プラーク / microarray / RT-PCR / Western blotting / 頚動脈狭窄 / プラーク / ANGPTL-1

Outline of Final Research Achievements

Carotid plaques from 18 endarterectomy patients were classified into high- and low-calcified plaques on the basis of Agatston calcium score. Microarray analysis demonstrated 93 angiogenesis or growth fac- tor–related transcripts that are reliably expressed (175 probe sets). Among them, angiopoietin-like protein 4 (ANGPTL4) expression was significantly elevated, whereas fibroblast growth factor receptor 2 (FGFR2) expression was significantly suppressed. Quantitative messenger RNA analysis was performed with real-time PCR. Augmented or decreased protein expression of each gene was confirmed by Western blotting analysis and immunohistochemistry. Conclusions: In high- calcified plaques, ANGPTL4 might be upregulated for antiangiogenic modulating function together with the downregulation of FGFR2, contributing to the stability of the plaques.

Research Products

• [Journal Article] Upregulation of ANGPTL4 messenger RNA and protein in severely calcified carotid plaque. (2014)
  • Author(s): Katano H, Yamada K
  • Journal Title: J Stroke Cerebrovasc Dis Volume: 23 Issue: 5 Pages: 933-947
  • DOI: 10.1016/j.jstrokecerebrovasdis.2013.07.046
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Revaluation of collateral pathways as escape routes from hyperemia/hyperperfusion following surgical treatment for carotid stenosis. (2012)
  • Author(s): 2. Katano H, Mase M, Sakurai K, Miyachi S, Yamada K.
  • Journal Title: Acta Neurochir (Wien) Volume: 154 Issue: 12 Pages: 2139-2149
  • DOI: 10.1007/s00701-012-1498-7
  • Peer Reviewed
• [Presentation] Differential gene expression in carotid plaques with calcification (2013)
  • Author(s): Katano H, Yamada K
  • Organizer: The 81th European Atherosclerosis Society Congress (EAS 2013)
  • Place of Presentation: Lyon Congress Centre (Lyon, France)
• [Presentation] 高度石灰化頸動脈粥種の網羅的遺伝子発現解析. (2013)
  • Author(s): 片野広之、間瀬光人、西川祐介、山田和雄.
  • Organizer: 第42回日本脳卒中の外科学会
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
• [Book] Adv Med Biol Vol.29 (Ed. Verhardt EL) (2011)
  • Author(s): Katano H, Mase M, Yamada K
  • Publisher: Evaluation for hardness of carotid plaque with Volume Score ­ Hounsfield Unit matrix and Calcium Score