Mechanism of blood coagulation disorder in atrial fibrillation

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09070
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kanazawa University
• Principal Investigator: Kato Takeshi 金沢大学, 先進予防医学研究科, 特任准教授 (90456418)
• Research Collaborator: YAEGASHI Takanori ; KANAMORI Naomi ; USUI Soichiro
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 心房細動 / 塞栓症

Outline of Final Research Achievements

Most strokes in patients with atrial fibrillation (AF) are believed to be cardioembolic, caused by the embolism of left atrial thrombi. As shown by the well-known Virchow triad, thrombus formation in the left atrium (LA) can result from decreased blood flow, increased endocardial dysfunction in the LA, and enhanced blood coagulability. We examined whether AF affects gene expression remotely in the liver, which is a major source of prothrombotic molecules. DNA microarray analysis revealed marked changes in the gene expression profile of human liver of patients with AF. The extrinsic prothrombin activation pathway showed the most prominent change. Twelve hours of rapid atrial pacing also markedly altered the gene expression profile of rat liver, which was eliminated by IL-6 neutralizing antibody. These findings suggest the presence of cadiohepatic interaction mediated by the IL-6/STAT3 signaling pathway in AF and AF-related thromboembolism.

Free Research Field

心臓不整脈

Academic Significance and Societal Importance of the Research Achievements

心房細動は高齢者の少なくとも5-10%に存在する不整脈で、その重大なな合併症として脳梗塞がある。この心原性脳梗塞は大変重篤で、ひとたび発症すると、約半数が死亡または麻痺により介助が必要な状態となることが報告されている。したがって、塞栓症のリスクを有する心房細動患者には抗凝固療法が行われるが、現在の抗凝固薬には出血という副作用が存在する。本研究は心房細動患者において血液が固まりやすくなる機序を、より根本的なレベルで解明した。これらの新しい知見は、より有効で安全性の高い脳梗塞予防法の開発につながると期待される。