Molecular mechanism of coronary microcirculation injury via endothelial Toll-like receptor in acute myocardial infarction

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08668
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Ehime University
• Principal Investigator: Kurata Mie 愛媛大学, プロテオサイエンスセンター, 講師 (80423440)
• Research Collaborator: Masumoto Junya ; Kaneko Naoe
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 急性心筋梗塞 / NETs / 内皮障害

Outline of Final Research Achievements

In acute myocardial infarction, there may occur a so-called microcirculatory disorder (no-reflow phenomenon) in which sufficient blood perfusion can not be obtained in the myocardium although the occlusion site is released. Applicants hypothesized that this phenomenon involves a mechanism by which neutrophils capture foreign pathogens by releasing a complex of their own nucleic acid and intracellular protein: neutrophil extracellular traps (NETs). We demonstrated NETs at the lesion site in acute myocardial infarction at autopsy. In addition, in order to clarify the endothelial receptor of nucleic acid complex NETs, we synthesized TLR in cell-free wheat germ system and revealed that it binds to known ligands.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

No-reflow現象の主たる病理像である内皮傷害は形態的検討はなされているもののその詳細な細胞伝達機構は未だ明らかではない。かしそれらの結果は依然no-reflow 現象を抑制する治療薬開発には結びついておらず、現在唯一のエビデンスを持った薬剤は血管拡張薬という対症療法のみである。いま、あらたな治療戦略が求められており、本研究がその一助となる可能性がある。