MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23940
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: University of Toyama
• Principal Investigator: Nakaoka Hideyuki 富山大学, 附属病院, 診療助手 (30725784)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 川崎病冠動脈瘤 / 血管微小粒子(EMP) / microRNA

Outline of Final Research Achievements

Endothelial microparticles (EMPs) modulate vasculitis during the acute phase of Kawasaki Disease (KD). KD is an acute inflammatory disease that takes the form of systemic vasculitis. EMPs are vesicles formed by cell membranes after endothelial activation. My research was to elucidate whether EMPs are involved in vasculitis in acute KD. In the KD patients with coronary artery lesions (CAL), EMPs rapidly increased after the initial treatment and was significantly higher compared with the Non-CAL (P<0.001). In the CAL, we identified 2 specific miRNAs, which were encapsulated in EMPs; hsa-miR-145-5p and hsa-miR-320a. In silico analysis revealed that they may regulate gene expression of inflammatory cytokines in monocytes and macrophages. EMPs are sensitive markers for the severity of endothelial dysfunction and vasculitis in the acute phase of KD. Hsa-miR-145-5p and hsa-miR-320a, encapsulated in EMPs, contribute to the progression of vascular inflammation in KD.

Free Research Field

小児循環器

Academic Significance and Societal Importance of the Research Achievements

国内外での研究動向は、川崎病急性期に血小板由来のMPsが上昇することを明らかにした論文も散見されるが、川崎病の病態となる全身性の中小動脈血管炎との関連は示されておらず、未だにCAL形成の病因/病態を明らかにするまでには至っていない。そこで我々は、川崎病急性期における血管内皮細胞傷害という側面から、我々が同定したCAL症例のEMPsに内在する特異的な2種類のmicroRNAを用い、この特異的な2種類のmicroRNAの局在と機能を解明し、CAL形成に関わるカスケードの解明およびCAL症例の早期診断かつ新たな治療法を開発することは極めて有意義であり、臨床応用に大いに期待できると考えている。