Comparative glycoproteomics for elucidating molecular mechanism of cardiac hypertrophy

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• 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 / 組織染色 / 心肥大モデル / 比較グライコーム解析 / 不死化心筋細胞 / レクチンアレイ / グライコプロテオミクス / 付加位置特異的糖鎖解析

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.

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。

Research Products

• [Journal Article] Deficiency of natriuretic peptide signaling promotes peripartum cardiomyopathy-like remodeling in the mouse heart. (2020)
  • Author(s): Otani K, Tokudome T, Kamiya CA, Mao Y, Nishimura H, Hasegawa T, Arai Y, Kaneko M, Shioi G, Ishida J, Fukamizu A, Osaki T, Nagai-Okatani C, Minamino N, Ensho T, Hino J, Murata S, Takegami M, Nishimura K, Kishimoto I, Miyazato M, Harada-Shiba M, Yoshimatsu J, Nakao K, Ikeda T, Kangawa K.
  • Journal Title: Circulation Volume: 141 Issue: 7 Pages: 571-588
  • DOI: 10.1161/circulationaha.119.039761
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Wisteria floribunda agglutinin staining for the quantitative assessment of cardiac fibrogenic activity in a mouse model of dilated cardiomyopathy (2019)
  • Author(s): Nagai-Okatani Chiaki、Nishigori Mitsuhiro、Sato Takashi、Minamino Naoto、Kaji Hiroyuki、Kuno Atsushi
  • Journal Title: Laboratory Investigation Volume: 99 Issue: 11 Pages: 1749-1765
  • DOI: 10.1038/s41374-019-0279-9
  • Peer Reviewed
• [Journal Article] LM-GlycomeAtlas Ver. 1.0: A Novel Visualization Tool for Lectin Microarray-Based Glycomic Profiles of Mouse Tissue Sections (2019)
  • Author(s): Nagai-Okatani Chiaki、Aoki-Kinoshita Kiyoko F、Kakuda Shuichi、Nagai Misugi、Hagiwara Kozue、Kiyohara Katsue、Fujita Noriaki、Suzuki Yoshinori、Sato Takashi、Angata Kiyohiko、Kuno Atsushi
  • Journal Title: Molecules Volume: 24 Issue: 16 Pages: 2962-2962
  • DOI: 10.3390/molecules24162962
  • Peer Reviewed / Open Access
• [Journal Article] Superiority of proatrial natriuretic peptide in the prognostic power in patients with acute decompensated heart failure on hospital admission: comparison with B-type natriuretic peptide and other natriuretic peptide forms (2019)
  • Author(s): Takashio Seiji、Takahama Hiroyuki、et al.
  • Journal Title: Open Heart Volume: 6 Issue: 2 Pages: e001072-e001072
  • DOI: 10.1136/openhrt-2019-001072
  • NAID: 120006878492
  • Peer Reviewed / Open Access
• [Journal Article] Change in the NT‐proBNP/Mature BNP Molar Ratio Precedes Worsening Renal Function in Patients With Acute Heart Failure: A Novel Predictor Candidate for Cardiorenal Syndrome (2019)
  • Author(s): Takahama Hiroyuki、Nishikimi Toshio、et al
  • Journal Title: Journal of the American Heart Association Volume: 8 Issue: 17
  • DOI: 10.1161/jaha.118.011468
  • NAID: 120006878493
  • Peer Reviewed / Open Access
• [Journal Article] 新規バイオマーカーの開発を目指した，拡張型心筋症における心筋線維化に伴うタンパク質上糖鎖変化の同定 (2019)
  • Author(s): 岡谷（永井）千晶
  • Journal Title: Medical science digest Volume: 45 Pages: 668-669
• [Journal Article] An Improved Method for Cell Type-Selective Glycomic Analysis of Tissue Sections Assisted by Fluorescence Laser Microdissection (2019)
  • Author(s): Nagai-Okatani Chiaki、Nagai Misugi、Sato Takashi、Kuno Atsushi
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 3 Pages: 700-700
  • DOI: 10.3390/ijms20030700
  • Peer Reviewed / Open Access
• [Journal Article] Current Technologies for Complex Glycoproteomics and Their Applications to Biology/Disease-Driven Glycoproteomics (2018)
  • Author(s): Narimatsu Hisashi、Kaji Hiroyuki、Vakhrushev Sergey Y.、Clausen Henrik、Zhang Hui、Noro Erika、Togayachi Akira、Nagai-Okatani Chiaki、Kuno Atsushi、Zou Xia、Cheng Li、Tao Sheng-Ce、Sun Yangyang
  • Journal Title: Journal of Proteome Research Volume: 17 Issue: 12 Pages: 4097-4112
  • DOI: 10.1021/acs.jproteome.8b00515
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ratio of pro-B-type natriuretic peptide (BNP) to total BNP is decreased in mild, but not severe, acute decompensated heart failure patients: A novel compensatory mechanism for acute heart failure (2018)
  • Author(s): Takahama Hiroyuki、Takashio Seiji、Nishikimi Toshio、Hayashi Tomohiro、Nagai-Okatani Chiaki、Nakagawa Yasuaki、Amaki Makoto、Ohara Takahiro、Hasegawa Takuya、Sugano Yasuo、Kanzaki Hideaki、Yasuda Satoshi、Kangawa Kenji、Minamino Naoto、Anzai Toshihisa
  • Journal Title: International Journal of Cardiology Volume: 258 Pages: 165-171
  • DOI: 10.1016/j.ijcard.2017.12.047
  • Peer Reviewed
• [Journal Article] Three molecular forms of atrial natriuretic peptides: quantitative analysis and biological characterization (2017)
  • Author(s): Nagai-Okatani Chiaki、Kangawa Kenji、Minamino Naoto
  • Journal Title: Journal of Peptide Science Volume: 23 Issue: 7-8 Pages: 486-495
  • DOI: 10.1002/psc.2969
  • Peer Reviewed
• [Journal Article] Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance. (2017)
  • Author(s): Kanai Y, Yasoda A, Mori KP, Watanabe-Takano H, Nagai-Okatani C, Yamashita Y, Hirota K, Ueda Y, Yamauchi I, Kondo E, Yamanaka S, Sakane Y, Nakao K, Fujii T, Yokoi H, Minamino N, Mukoyama M, Mochizuki N, Inagaki N.
  • Journal Title: Journal of Clinical Investigation Volume: 127 Issue: 11 Pages: 4136-4147
  • DOI: 10.1172/jci94912
  • Peer Reviewed / Open Access
• [Journal Article] Impact of continuous reduction in B-Type natriuretic peptide bioactivity during hospitalization in patients with advanced heart failure (2017)
  • Author(s): Hiroyuki Takahama, Seiji Takashio, Tomohiro Hayashi, Chiaki Nagai-Okatani, Toshio Nishikimi, Yasuaki Nakagawa, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Kenji Kangawa, Naoto Minamino, Toshihisa Anzai
  • Journal Title: Circulation Volume: 136
  • Open Access
• [Presentation] 心筋線維化の定量的評価法のための新規糖鎖マーカー開発への取り組み (2019)
  • Author(s): 岡谷千晶、錦織充広、佐藤隆、南野直人、梶裕之、久野敦
  • Organizer: 第18回 産総研・産技連LS-BT合同研究発表会
• [Presentation] 心筋線維化の定量的評価法のための新規糖鎖マーカー開発に向けた、拡張型心筋症モデルマウス心臓のグライコーム・グライコプロテオーム解析 (2019)
  • Author(s): 岡谷千晶、錦織充広、佐藤隆、南野直人、梶裕之、久野敦
  • Organizer: 日本プロテオーム学会2019年大会
• [Presentation] Glycomic and glycoproteomic approaches for development of novel glyco-biomarkers of cardiac fibrogenesis using a mouse model of dilated cardiomyopathy (2019)
  • Author(s): Nagai-Okatani Chiaki、Nishigori Mitsuhiro、Sato Takashi、Minamino Naoto、Kaji Hiroyuki、Kuno Atsushi
  • Organizer: 18th Human Proteome Organization World Congress (HUPO2019)
  • Int'l Joint Research
• [Presentation] Visualization of a lectin microarray-based dataset for mouse tissue glycome mapping by a novel online tool, LM-GlycomeAtlas (2019)
  • Author(s): Nagai-Okatani Chiaki、Aoki-Kinoshita Kiyoko F、Kakuda Shuichi、Nagai Misugi、Hagiwara Kozue、Kiyohara Katsue、Fujita Noriaki、Suzuki Yoshinori、Sato Takashi、Angata Kiyohiko、Kuno Atsushi
  • Organizer: 2nd Australasian Glycoscience Symposium (2nd AGS)
  • Int'l Joint Research
• [Presentation] Recent progresses on lectin array towards glyco-target discovery (2019)
  • Author(s): Kuno Atsushi、Nagai-Okatani Chiaki、Shimazaki Hiroko、Matsuda Atsushi、Wagatsuma Takanori
  • Organizer: 11th ACGG
  • Int'l Joint Research
• [Presentation] Identification of Wisteria Floribunda Agglutinin as a Specific Lectin for Detection of Cardiac Fibrosis in a Dilated Cardiomyopathy Mouse Model Using Lectin Microarray-Based Glycomic Analysis (2019)
  • Author(s): 岡谷千晶、錦織充広、佐藤隆、南野直人、梶裕之、久野敦
  • Organizer: 第83回日本循環器学会学術集会
  • Invited
• [Presentation] An improved method for cell type-specific glycomic analysis of formalin-fixed paraffin-embedded tissue sections in combination with histochemical staining (2018)
  • Author(s): Chiaki Nagai-Okatani, Misugi Nagai, Atsushi Kuno
  • Organizer: Mass Spectrometry and Proteomics 2018
• [Presentation] Association of ratio of proBNP to total BNP with heart failure severity: A novel compensatory mechanism for acute heart failure (2018)
  • Author(s): 高濱博幸、高潮征爾、錦見俊雄、林友鴻、岡谷千晶、中川靖章、天木誠、大原貴裕、長谷川拓也、菅野康夫、神﨑秀明、安田聡、寒川賢治、南野直人、安斉俊久
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] ProBNP ratio to total BNP predicts future cardiac reverse remodeling in acute heart failure patients with reduced ejection fraction (2018)
  • Author(s): 高濱博幸、高潮征爾、錦見俊雄、林友鴻、岡谷千晶、中川靖章、濱谷康弘、岡田厚、天木誠、長谷川拓也、菅野康夫、神﨑秀明、安田聡、寒川賢治、南野直人、安斉俊久
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] レーザーマイクロダイセクション－レクチンマイクロアレイによるマウス組織グライコームマッピング (2017)
  • Author(s): 岡谷千晶、角田修一、Xia Zou、吉田真樹、佐藤隆、松田厚志、萩原梢、清原克恵、板倉、陽子、野呂絵里花、豊田雅士、Yan Zhang、成松久、久野敦
  • Organizer: 日本プロテオーム学会2017年大会
• [Presentation] A comprehensive analysis of glycome profiles on formalin-fixed paraffin-embedded mouse tissue sections (2017)
  • Author(s): Chiaki Nagai-Okatani, Shuichi Kakuda, Xia Zou, Maki Yoshida, Takashi Sato, Atsushi Matsuda, Kozue Hagiwara, Katsue Kiyohara, Yoko Itakura, Erika Noro, Masashi Toyoda, Sheng-Ce Tao, Yan Zhang, Hisashi Narimatsu, Atsushi Kuno
  • Organizer: 16th Human Proteome Organization World Conress
  • Int'l Joint Research
• [Presentation] Development of site-specific glycome analysis method of complex glycoproteome (2017)
  • Author(s): Hiroyuki Kaji, Azusa Tomioka, Chiaki Nagai-Okatani, Erika Noro, Toshihide Shikanai, Hisashi Narimatsu.
  • Organizer: 16th Human Proteome Organization World Conress
  • Int'l Joint Research
• [Presentation] 複雑性の極み: 糖鎖修飾状態の解析への挑戦 (2017)
  • Author(s): 梶裕之、富岡あづさ、野呂絵里花、岡谷千晶、藤田弥佳、助川昌子、成松久
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] C型ナトリウム利尿ペプチドに対する高感度特異的測定法の開発と血中および組織中の濃度測定 (2017)
  • Author(s): 松尾文香、岡谷千晶、寒川賢治、南野直人
  • Organizer: 第90回日本内分泌学会学術総会
• [Presentation] Impact of continuous reduction in B-Type natriuretic peptide bioactivity during hospitalization in patients with advanced heart failure (2017)
  • Author(s): Hiroyuki Takahama, Seiji Takashio, Tomohiro Hayashi, Chiaki Nagai-Okatani, Toshio Nishikimi, Yasuaki Nakagawa, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Kenji Kangawa, Naoto Minamino, Toshihisa Anzai
  • Organizer: American Heart Association Scientific Sessions 2017
  • Int'l Joint Research
• [Book] 病理と臨床 特集「パラフィン包埋標本でできる分子病理解析 Up To Date」パラフィン包埋標本を用いた比較組織グライコーム解析 (2017)
  • Author(s): 松田厚志、岡谷千晶、久野敦
  • Total Pages: 7
  • Publisher: 文光堂