心不全をターゲットとしたバイオマーカーへのマイクロＲＮＡの応用

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25461075
• Research Institution: Fujita Health University
• Principal Investigator: 井澤 英夫 藤田保健衛生大学, 医学部, 教授 (80402569)
• Co-Investigator(Kenkyū-buntansha): 横井 博厚 藤田保健衛生大学, 医学部, 講師 (20644876) ; 尾崎 行男 藤田保健衛生大学, 医学部, 教授 (50298569) ; 藤原 稚也 藤田保健衛生大学, 医学部, 講師 (60644870)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 循環器 / 心不全 / マイクロRNA / バイオマーカー

Outline of Annual Research Achievements

二次性心筋症の心臓サルコイドーシスの病態および治療法は未だ確立していない。サルコイドーシスは原因不明の全身疾患で心臓の他に、肺、 眼、皮膚、神経、消化管、筋、腎、骨等に壊死を伴わない類上皮細胞肉芽腫が存在し、様々な臓器障害を引き起こす難病である。心臓病変はサルコイドーシスの主要な死因で心不全や致死性不整脈を引き起こす。サルコイドーシスの診断には肺や皮膚、消化管等の全身のいずれかの臓器で組織診断を行い類上皮細胞肉芽腫病変を検出をすることに基づいて確定されるが、全身の臓器障害を伴わない心臓限局性サルコイドーシスが存在し、心不全症例で心臓限局性サルコイドーシスを疑う場合は侵襲的な心筋生検を実施する必要がある。
最近、マイクロRNA (miRNA)が血中にも分泌され、臓器間での遺伝子発現調整ネットワークで重要な役割を演じている可能性が示唆されていることから、今回私たちは心臓サルコイドーシス症例の末梢血液中miRNAを測定して、特異的なmiRNAを同定し、バイオマーカーとしての臨床応用や治療ターゲットとしての確立を目指して研究を行った。心臓サルコイドーシス5例と健常者3例から血液を採取して389個の血液中miRNA発現レベルをマイクロアレイを用いて網羅的にプロファイリングした。その結果、健常者と比較して心臓サルコイドーシスでは200個の血液中miRNAが有意に (p <0.01) 異常発現していた。200個のmiRNAの中で心臓サルコイドーシスでは13個のmiRNAが強力に (ratio> 4) 発現が低下し、27個のmiRNAが発現が上昇していた。以上から心臓サルコイドーシスの診断的血液バイオマーカーとして、これらのmiRNAが臨床応用できる可能性が示唆された。

Research Products

• [Journal Article] Clinical Characteristics and Long-Term Outcomes of Hypertrophic Cardiomyopathy. (2015)
  • Author(s): Yoshinaga M, Yoshikawa D, Ishii H, Hirashiki A, Okumura T, Kubota A, Sakai S, Harada K, Somura F, Mizuno T, Fujiwara W, Yokoi H, Hayashi M, Ishii J, Ozaki Y, Murohara T, Yoshida Y, Amano T, Izawa H.
  • Journal Title: International Heart Journal Volume: 56 Pages: 415-420
  • DOI: 10.1536/ihj.14-418
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Takotsubo Cardiomyopathy with Involvement Delayed-onset Rhabdomyolysis and Acute Kidney Injury after Rosuvastatin Treatment. (2015)
  • Author(s): Kamada T, Hayashi M, Yokoi H, Fujiwara W, Yoshikawa D, Mukaide D, Sugishita Y, Yoshinaga M, Ito T, Ozaki Y, Izawa H.
  • Journal Title: Internal Medicine Volume: 54 Pages: 31-35
  • DOI: 10.2169/internalmedicine.54.3239
  • Peer Reviewed / Open Access
• [Journal Article] Prescription patterns of oral anticoagulants for patients with non-valvular atrial fibrillation: experience at a Japanese single institution. (2015)
  • Author(s): Tagaya M, Yoshikawa D, Sugishita Y, Yamauchi F, Ito T, Kamada T, Yoshinaga M, Mukaide D, Fujiwara W, Yokoi H, Hayashi M, Watanabe E, Ishii J, Ozaki Y, Izawa H.
  • Journal Title: Heart and Vessels Volume: Epub ahead of print Pages: 0-0
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Combined Assessment of Acute Kidney Injury and Increased Plasma Concentration of D-dimer Is Useful for Evaluating 1-year Mortality in Patients Hospitalized to Coronary Care Units. (2015)
  • Author(s): Matsui S, Ishii J, Okuyama R, Takahashi H, Kawai H, Muramatsu T, Yamada A, Motoyama S, Naruse H, Hayashi M, Izawa H, Ozaki Y.
  • Organizer: Scientific Sessions 2015, American Heart Association.
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Combined Assessment of High-Sensitive Troponin I and N-Terminal Pro-B-Type Natriuretic Peptide Levels Improves the Prediction of Cardiovascular Event in Outpatients With Hypertension. (2015)
  • Author(s): Matsui S, Ishii J, Okuyama R, Takahashi H, Kawai H, Muramatsu T, Yamada A, Motoyama S, Naruse H, Hayashi M, Izawa H, Ozaki Y.
  • Organizer: Scientific Sessions 2015, American Heart Association.
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Prognostic Value of Combined Assessment of Oxidized Lipoprotein (a) and Estimated Glomerular Filtration Rate in Patients Undergoing Elective Coronary Angiography for Suspected Coronary Artery Disease. (2015)
  • Author(s): Naruse H, Ishii J, Okuyama R, Ohta M, Kawai H, Okumura M, Muramatsu T, Hayashi M, Matsui S, Motoyama S, Izawa H, Ozaki Y.
  • Organizer: Scientific Sessions 2015, American Heart Association.
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] 心不全と糖尿病 (2015)
  • Author(s): 井澤英夫
  • Organizer: 第1回日本心臓リハビリテーション学会東海地方会
  • Place of Presentation: 岐阜市、じゅうろくプラザ
  • Year and Date: 2015-10-18 – 2015-10-18
  • Invited
• [Presentation] 心不全の心臓リハビリテーション (2015)
  • Author(s): 井澤英夫
  • Organizer: 第38回日本リハビリテーション医学会九州地方会
  • Place of Presentation: 那覇市、てんぶす那覇
  • Year and Date: 2015-10-04 – 2015-10-04
  • Invited
• [Presentation] 心不全の長期予後と心臓リハビリテーション (2015)
  • Author(s): 井澤英夫、河野裕治、粥川知子、青柳陽一郎、才藤栄一、吉川大治、藤原稚也、山田純生
  • Organizer: 第21回日本心臓リハビリテーション学会学術集会
  • Place of Presentation: 福岡市、福岡国際会議場
  • Year and Date: 2015-07-18 – 2015-07-19
  • Invited
• [Presentation] Combined Assessment of High-Sensitive Troponin I and NT-proBNP Improves Prediction of Future Admission for Heart Failure in Outpatients with CKD. (2015)
  • Author(s): Yoshihisa Mori, Junichi Ishii, Hiroshi Takahashi, Ryunosuke Okuyama, Tousei Hashimoto, Hideki Kawai, Takashi Muramatsu, Hiroyuki Naruse, Sadako Motoyama, Shigeru Matsui, Midori Hasegawa, Hideo Izawa, Yukio Yuzawa, Yukio Ozaki.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2015-04-24 – 2015-04-28
  • Int'l Joint Research
• [Presentation] Combined Assessment of Plasma D-Dimer and Estimated GFR Improves Prediction of Mortality in Patients with Suspected Coronary Artery Disease. (2015)
  • Author(s): Hiroyuki Naruse, Junichi Ishii, Ryunosuke Okumura, Masaya Ohta, Masanori Okumura, Takashi Muramatsu, Shigeru Matsui, Hideo Izawa, Yukio Ozaki.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2015-04-24 – 2015-04-28
  • Int'l Joint Research
• [Presentation] Combined Assessment of Serum Neutrophil Gelatinase-Associated Lipocalin and NT-proBNP on Admission Improves Prediction of Mortality in Patients Hospitalized to CCUs. (2015)
  • Author(s): Ryunosuke Okuyama, Junichi Ishii, Tousei Hashimoto, Hideki Kawai, Takashi Muramatsu, Hiroyuki Naruse, Shigeru Matsui, Sadako Motoyama, Yoshihisa Mori, Hideo Izawa, Yukio Ozaki.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2015-04-24 – 2015-04-28
  • Int'l Joint Research
• [Presentation] Inhibitory Factors for a Prescription of Novel Oral Anti-Coagulant Agents for Non-Valvular Atrial Fibrillation: An Analysis from the ‘Real World’. (2015)
  • Author(s): Yoshinori Sugishita, Daiji Yoshikawa, Takehiro Ito, Tomohito Kamada, Masataka Yoshinaga, Daisuke Mukaide, Wakaya Fujiwara, Hiroatsu Yokoi, Mutsuharu Hayashi, Toyoaki Murohara, Yukio Ozaki, Hideo Izawa.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2015-04-24 – 2015-04-28
  • Int'l Joint Research
• [Presentation] Plasma Indoxyl Sulfate Levels Predict Long-term Clinical Outcomes in Patients with Coronary Artery Disease. (2015)
  • Author(s): Daiji Yoshikawa, Hideki Ishii, Susumu Suzuki, Kyosuke Takeshita, Mutsuharu Hayashi, Hideo Izawa, Yukio Ozaki, Toyoaki Murohara.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2015-04-24 – 2015-04-28
  • Int'l Joint Research
• [Presentation] Combination of Admission Urinary Albumin and Neutrophil Gelatinase-Associated Lipocalin Improves Prediction of Acute Kidney Injury in Patients Hospitalized to CCUs. (2015)
  • Author(s): Tousei Hashimoto, Junichi Ishii, Ryunosuke Okuyama, Hiroyuki Naruse, Yoshihisa Mori, Shigeru Matsui, Hideo Izawa, Yukio Ozaki.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2015-04-24 – 2015-04-26
  • Int'l Joint Research
• [Presentation] Combination of High-Sensitive Troponin and N-Terminal Pro-B-Type Natriuretic Peptide Improves Prediction of Future Admission for Heart Failure in Hypertensive Patients. (2015)
  • Author(s): Junichi Ishii, Ryunosuke Okuyama, Hideki Kawai, Takashi Muramatsu, Hiroyuki Naruse, Sadako Matoyama, Shigeru Matsui, Eiichi Watanabe, Hideo Izawa, Yukio Ozaki.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2015-04-24 – 2015-04-26
  • Int'l Joint Research
• [Presentation] Predictors for In-hospital Clinical Outcome in Patients Prescribed Tolvaptan for Their Worsening Heart Failure. (2015)
  • Author(s): Takehiro Ito, Daiji Yoshikawa, Mutsuharu Hayashi, Wakaya Fujiwara, Daisuke Mukaide, Yoshinori Sugishita, Toyoaki Murohara, Junichi Ishii, Yukio Ozaki, Hideo Izawa.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2015-04-24 – 2015-04-26
  • Int'l Joint Research
• [Presentation] Combined Assessment of High-Sensitive Troponin I and NT-proBNP Improves Prediction of Future Admission for Heart Failure Outpatients with Hypertension. (2015)
  • Author(s): Shigeru Matsui, Junichi Ishii, Ryunosuke Okuyama, Masanori Okuyama, Tousei Hashimoto, Hideki Kawai, Takashi Muramatsu, Hiroyuki Naruse, Yoshihisa Mori, Sadako Motoyama, Hideo Izawa, Yukio Ozaki.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2015-04-24 – 2015-04-26
  • Int'l Joint Research