Establishment of molecular forensic diagnosis of cardiac sudden death

• Project/Area Number: 15H04798
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: Ishida Yuko 和歌山県立医科大学, 医学部, 講師 (10364077)
• Co-Investigator(Kenkyū-buntansha): 野坂 みずほ 和歌山県立医科大学, 医学部, 助教 (00244731) ; 木村 章彦 和歌山県立医科大学, 医学部, 博士研究員 (60136611)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 突然死 / ケモカイン / 大動脈瘤 / 法医病理学

Outline of Final Research Achievements

In the aortic tissue of the mouse aortic aneurysm model, Ccl3 gene expression was markedly enhanced. When aortic aneurysms were induced using Ccl3 － / － mice, aortic aneurysm formation was significantly exacerbated compared to wild-type mice. Moreover, Ccr1 － / － mice showed aortic aneurysm formation similar to wild type, while Ccr5 － / － mice showed aortic aneurysm formation similar to Ccl3 － / － mice. Therefore, it was suggested that CCL3-CCR5 system plays an important role in aortic aneurysm formation. When the expression of CCL3 was examined by immunostaining using the aortic aneurysm collected in a forensic autopsy case, it was found to be expressed in CD68 positive macrophages.

Academic Significance and Societal Importance of the Research Achievements

本研究は，心筋梗塞および大動脈瘤・大動脈解離におけるサイトカイン・ケモインの病態生理学的役割を解明することによりサイトカイン・ケモカインを指標とする突然死の分子法医診断法を確立することを目的とするものである．最終的に，突然死におけるサイトカイン・ケモカインを指標とする分子法医診断基準の確立を目指すものであり，本研究成果より，ケモカインCCL3の発現亢進が新規分子指標となり得る可能性を見出した．

Research Products

• [Presentation] The absence of CCL3 exaggerated CaCl2-induced aortic aneurysm (2018)
  • Author(s): Yuko Ishida
  • Organizer: IALM
  • Int'l Joint Research
• [Presentation] Prevention of CaCl2-induced aortic inflammation and subsequent aneurysm formation by a typical inflammatory chemokine, CCL3 (2018)
  • Author(s): Yuko Ishida
  • Organizer: 日本炎症再生医学会
• [Presentation] CaCl2誘発大動脈瘤におけるケモカインCCL3の病態生理学的役割 (2018)
  • Author(s): 石田裕子
  • Organizer: 日本法医病理学会
• [Presentation] The pathophysiological roles of CCL3 in CaCl2-induced aneurysm (2016)
  • Author(s): 石田裕子
  • Organizer: 第100次日本法医学会学術全国集会
  • Place of Presentation: 東京