Comparative glycoproteomics for elucidating molecular mechanism of cardiac hypertrophy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K18414
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine; Pathological medical chemistry
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Okatani Chiaki 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (30633648)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 疾患関連糖鎖変化 / 心不全 / 心肥大 / 心筋線維化 / 糖鎖プロファイル解析 / グライコプロテオーム解析

Outline of Final Research Achievements

It is of significant importance to elucidate the molecular mechanisms underlying cardiac hypertrophy and consequent heart failure, especially for the development of novel strategies for the therapeutic treatments. In this study, we aimed to comprehensively characterize cardiac hypertrophy/heart failure-related alterations in protein glycosylations, which have pivotal roles in the modulation of protein functions. We characterized glycosylation alterations in the cell surface of cardiac myocytes treated with hypertrophic agonists, which exhibited discrete consequences depending on the type of agonists. Using a heart failure mouse model, we also identified cardiac fibrosis-related glycosylation alterations, which had discrete characteristics from the changes observed in cardiac myocytes. These findings are expected to contribute to elucidation of the significance of protein glycosylations in the molecular mechanisms underlying myocardial impairment that leads to heart failure.

Free Research Field

糖鎖生物学、グライコミクス、グライコプロテオミクス

Academic Significance and Societal Importance of the Research Achievements

本研究では、心肥大・心不全と関連した糖鎖変化およびその変化を示す糖タンパク質群を網羅的に明らかにした。本成果により、これらの糖鎖変化を指標とした新たな診断法の開発への応用が期待できる。また、これらの糖鎖変化とタンパク質の機能異常との関連性を詳細に調べることで、新たな心肥大・心不全の発症・進展メカニズムが明らかになる可能性がある。