Neoatherosclerosisの本態解明と新規治療法の開発

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25293182
• Research Institution: Kyoto University
• Principal Investigator: 木村 剛 京都大学, 医学(系)研究科(研究院), 教授 (80359786)
• Co-Investigator(Kenkyū-buntansha): 尾野 亘 京都大学, 医学(系)研究科(研究院), 准教授 (00359275) ; 今井 逸雄 京都大学, 医学(系)研究科(研究院), 助教 (10625677) ; 齋藤 成達 京都大学, 医学(系)研究科(研究院), 助教 (20467484) ; 西 英一郎 京都大学, 医学(系)研究科(研究院), 准教授 (30362528) ; 牧山 武 京都大学, 医学(系)研究科(研究院), 助教 (30528302)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: neoatherosclerosis / 血栓 / ステント

Outline of Annual Research Achievements

①BMSおよびDES留置を行った症例でのステント治療部位の解析：さらにステント留置後の長期フォロー例を中心にデータの蓄積を行っている。DES(シロリムスステント)を植え込んだ5712例(7838病変)の病変を検討したところ、ステント周囲の造影剤の染み出し現象(PSS)は184例(3.2%)(194病変(2.5%))に認められた。PSSに対する危険因子としては完全閉塞、左前下降枝病変があった。超遅延性ステント血栓症はPSS症例において5.3%(それ以外は0.7%)と多いことが判明した。
②BMSおよびDES留置後、VLSTを発症した患者の吸引血栓の病理的分子生物学的検討： これまでに、VLSTの病理組織内において、13%に動脈硬化巣の組織の一部を認め、neoatherosclerosisがVLSTの原因をなしている可能性が示唆されたが、さらに詳細な基礎的検討を行っている。
③ステント留置後の剖検症例の集積：さらに症例を増加させている。
④血管内皮を早期に増殖、障害血管の再内皮化をはかるステントの開発：早期の臨床応用を視野に、ウイルスなどのベクターを使用せず、miR-126を局所で過剰発現させるための2本鎖合成RNAを設計した。これは、22塩基のmiR-126が選択的にDicerによって切断され、マイクロRNAの機能を発揮するRISCコンプレックスに取り込まれるように、両端に塩基を付加し、27塩基の2本鎖RNAとしたもので、さらに、この2本鎖合成RNAを乳酸・グリコール酸共重合体（PLGA）ナノ粒子に含有させ、ステントに電気的に均一にコーティングし、局所で徐放化できるステントを開発した。ウサギの腸骨動脈において、miR-126搭載ステントにおいて、コントロールRNAと比較して、有意に再狭窄予防効果を認めた。さらにブタ冠動脈モデルにおいて検討を続けている。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Causes of Carryover

27年度が最終年度であるため、記入しない。

Expenditure Plan for Carryover Budget

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes. (2016)
  • Author(s): Funakoshi S, Miki K, Takaki T, Okubo C, Hatani T, Chonabayashi K, Nishikawa M, Takei I, Oishi A, Narita M, Hoshijima M, Kimura T, Yamanaka S, Yoshida Y.
  • Journal Title: Sci Rep. Volume: 6 Pages: 19111
  • DOI: 10.1038/srep19111.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Duration of Prehospital Resuscitation Efforts After Out-of-Hospital Cardiac Arrest. (2016)
  • Author(s): Nagao K, Nonogi H, Yonemoto N, Gaieski DF, Ito N, Takayama M, Shirai S, Furuya S, Tani S, Kimura T, Saku K; Japanese Circulation Society With Resuscitation Science Study (JCS-ReSS) Group*.
  • Journal Title: Circulation Volume: 133 Pages: 1386-96
  • DOI: 10.1161/CIRCULATIONAHA.115.018788.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 1-year outcomes with the Absorb bioresorbable scaffold in patients with coronary artery disease: a patient-level, pooled meta-analysis. (2016)
  • Author(s): Stone GW, Gao R, Kimura T, Kereiakes DJ, Ellis SG, Onuma Y, Cheong WF, Jones-McMeans J, Su X, Zhang Z, Serruys PW.
  • Journal Title: Lancet Volume: 387 Pages: 1277-89
  • DOI: 10.1016/S0140-6736(15)01039-9.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The renin-angiotensin system promotes arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy. (2016)
  • Author(s): Yamada C, Kuwahara K, Yamazaki M, Nakagawa Y, Nishikimi T, Kinoshita H, Kuwabara Y, Minami T, Yamada Y, Shibata J, Nakao K,Cho K, Arai Y, Honjo H, Kamiya K, Nakao K, Kimura T.
  • Journal Title: Cardiovasc Res. Volume: 109 Pages: 162-73
  • DOI: 10.1093/cvr/cvv248
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of Age and Sex on Clinical Outcomes after Percutaneous Coronary Intervention Relative to Coronary Artery Bypass Grafting in Patients with Triple Vessel Coronary Artery Disease. (2016)
  • Author(s): Yamaji K, Shiomi H, Morimoto T, Nakatsuma K, Toyota T, Ono K, Furukawa Y, Nakagawa Y, Kadota K, Ando K, Shirai S, Onodera T, Watanabe H, Natsuaki M, Sakata R, Hanyu M, Nishiwaki N, Komiya T, Kimura T.
  • Journal Title: Circulation Volume: 115 Pages: 020955
  • DOI: 10.1161/CIRCULATIONAHA.115.020955
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan. (2015)
  • Author(s): Kimura T, Kozuma K, Tanabe K, Nakamura S, Yamane M, Muramatsu T, Saito S, Yajima J, Hagiwara N, Mitsudo K, Popma JJ, Serruys PW, Onuma Y, Ying S, Cao S, Staehr P, Cheong WF, Kusano H, Stone GW; ABSORB Japan Investigators.
  • Journal Title: Eur Heart J. Volume: 36 Pages: 3332-42
  • DOI: 10.1093/eurheartj/ehv435.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. (2015)
  • Author(s): Cassese S, Byrne RA, Ndrepepa G, Kufner S, Wiebe J, Repp J, Schunkert H, Fusaro M, Kimura T, Kastrati A.
  • Journal Title: Lancet Volume: 387 Pages: 537-544
  • DOI: 10.1016/S0140-6736(15)00979-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High-density lipoprotein cholesterol levels and cardiovascular outcomes in Japanese patients after percutaneous coronary intervention: a report from the CREDO-Kyoto registry cohort-2. (2015)
  • Author(s): Izuhara M, Ono K, Shiomi H, Morimoto T, Furukawa Y, Nakagawa Y, Shizuta S, Tada T, Tazaki J, Horie T, Kuwabara Y, Baba O, Nishino T, Kita T, Kimura T; CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators.
  • Journal Title: Atherosclerosis Volume: 242 Pages: 632-8
  • DOI: 10.1016/j.atherosclerosis.2015.05.010.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial. (2015)
  • Author(s): Kaitani K, Inoue K, Kobori A et al.
  • Journal Title: Eur Heart J. Volume: 37 Pages: 610-8
  • DOI: 10.1093/eurheartj/ehv501.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure. (2015)
  • Author(s): Kawamoto A, Kato T, Shioi T, Okuda J, Kawashima T, Tamaki Y, Niizuma S, Tanada Y, Takemura G, Narazaki M, Matsuda T, Kimura T.
  • Journal Title: PLoS One Volume: 10 Pages: e0117091
  • DOI: 10.1093/eurheartj/ehv501.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial (2015)
  • Author(s): Kobori A, Shizuta S, Inoue K et al.
  • Journal Title: Eur Heart J. Volume: 36 Pages: 3276-87
  • DOI: 10.1093/eurheartj/ehv457.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression Patterns of miRNA-423-5p in the Serum and Pericardial Fluid in Patients Undergoing Cardiac Surgery. (2015)
  • Author(s): Miyamoto S, Usami S, Kuwabara Y, Horie T, Baba O, Hakuno D, Nakashima Y, Nishiga M, Izuhara M, Nakao T, Nishino T, Ide Y,Nakazeki F, Wang J, Ueyama K, Kimura T, Ono K.
  • Journal Title: PLoS One Volume: 10 Pages: e0142904
  • DOI: 10.1371/journal.pone.0142904
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA-33a/b in lipid metabolism – novel “thrifty” models. (2015)
  • Author(s): Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Yokode M, Kita T, Kimura T.
  • Journal Title: Circ J. Volume: 79 Pages: 278-84
  • DOI: 10.1253/circj.CJ-14-1252.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comparison of Five-Year Outcome of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Triple-Vessel Coronary Artery Disease (from the Coronary Revascularization DemonstratingOutcome Study in Kyoto PCI/CABG Registry Cohort-2). (2015)
  • Author(s): Shiomi H, Morimoto T, Furukawa Y, Nakagawa Y, Tazaki J, Sakata R, Okabayashi H, Hanyu M, Shimamoto M, Nishiwaki N, Komiya T,Kimura T; CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators.
  • Journal Title: Am J Cardiol. Volume: 116 Pages: 59-65
  • DOI: 10.1016/j.amjcard.2015.03.040
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Initial Surgical Versus Conservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis. (2015)
  • Author(s): Taniguchi T, Morimoto T, Shiomi H et al.
  • Journal Title: J Am Coll Cardiol. Volume: 66 Pages: 2827-38
  • DOI: 10.1016/j.jacc.2015.10.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Meta-analysis of long-term clinical outcomes of everolimus-eluting stents. (2015)
  • Author(s): Toyota T, Shiomi H, Morimoto T, Kimura T.
  • Journal Title: Am J Cardiol. Volume: 116 Pages: 187-94
  • DOI: 10.1016/j.amjcard.2015.03.059
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Antiplatelet therapy discontinuation and the risk of serious cardiovascular events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort-2. (2015)
  • Author(s): Watanabe H, Morimoto T, Natsuaki M et al.
  • Journal Title: PLoS One Volume: 10 Pages: e0124314
  • DOI: 10.1371/journal.pone.0124314
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical efficacy of thrombus aspiration on 5-year clinical outcomes in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention. (2015)
  • Author(s): Watanabe H, Shiomi H, Nakatsuma K et al.
  • Journal Title: J Am Heart Assoc. Volume: 4 Pages: e001962
  • DOI: 10.1161/JAHA.115.001945.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Influence of Sex on Long-Term Outcomes After Implantation of Bare-Metal Stent: A Multicenter Report From the Coronary Revascularization Demonstrating Outcome Study-Kyoto (CREDO-Kyoto) Registry Cohort-1. (2015)
  • Author(s): Yamaji K, Shiomi H, Morimoto T, Toyota T, Ono K, Furukawa Y, Nakagawa Y, Kadota K, Ando K, Shirai S, Kato M, Takatsu Y, Doi O,Kambara H, Suwa S, Onodera T, Watanabe H, Natsuaki M, Kimura T.
  • Journal Title: Circulation Volume: 132 Pages: 2323-33
  • DOI: 10.1161/CIRCULATIONAHA.115.017168.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] High-density Lipoprotein Cholesterol Levels and Cardiovascular Outcomes in Japanese Patients after Percutaneous Coronary Intervention from the CREDO-Kyoto Registry Cohort-2. (2016)
  • Author(s): Izuhara M.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際センター外（仙台市）
  • Year and Date: 2016-03-18 – 2016-03-20
• [Presentation] MicroRNA-451 Exacerbates Lipotoxicity in Cardiomyocytes and High-Fat Diet-Induced Cardiac Hypertrophy in Mice through Suppression of the LKB1/AMPK Pathway. (2016)
  • Author(s): Ono K.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際センター外（仙台市）
  • Year and Date: 2016-03-18 – 2016-03-20
• [Presentation] CREDO-Kyoto PCI/CABG Registry Cohort-2Investigators. High-density lipoprotein cholesterol levels and cardiovascular outcomes in Japanese patients after percutaneous coronary intervention: A report from the CREDO-Kyoto registry cohort-2. (2015)
  • Author(s): Izuhara M, Ono K, Shiomi H, Morimoto T, Furukawa Y, Nakagawa Y, Shizuta S, Tada T, Tazaki J, Horie T, Kuwabara Y, Baba O, Nishino T, Kita T, Kimura T.
  • Organizer: American Heart Association Annual Scientific Sessions 2015
  • Place of Presentation: Orlando, Florida（USA）
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Reappraisal of antithrombotic-regimen in patients with atrial fibrillation after drug-eluting stent implantation. When to skip aspirin? Look back on the case-experience. (2015)
  • Author(s): Toyota T.
  • Organizer: American Heart Association Annual Scientific Sessions 2015
  • Place of Presentation: Orlando, Florida（USA）
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Session IV. DES Thrombosis and Restenosis. (2015)
  • Author(s): Kimura T.
  • Organizer: TCT 2015
  • Place of Presentation: Orlando, Florida（USA）
  • Year and Date: 2015-10-11 – 2015-10-15
  • Int'l Joint Research
• [Presentation] Plenary Session VII. First Report Investigations. (2015)
  • Author(s): Kimura T.
  • Organizer: TCT 2015
  • Place of Presentation: Orlando, Florida（USA）
  • Year and Date: 2015-10-11 – 2015-10-15
  • Int'l Joint Research
• [Presentation] Successful Percutaneous Closure of Large and Maialigment Atrial Septal Defects with Plumonary Hypertension. (2015)
  • Author(s): Imai M, Watanabe S, Toyoda T, Kimura T.
  • Organizer: CSI 2015
  • Place of Presentation: Frankfrut（Germany）
  • Year and Date: 2015-08-30 – 2015-09-03
  • Int'l Joint Research
• [Presentation] ABSORB Japan. 12-month clinical and 13-month angiographic outcomes from a randomized trial evaluating the Absorb Bioresorbable Vascular Scaffold vs_ metallic DES in de novo native coronary artery lesions. (2015)
  • Author(s): Kimura T.
  • Organizer: ESC CONGRESS 2015
  • Place of Presentation: London（UK）
  • Year and Date: 2015-08-29 – 2015-09-02
  • Int'l Joint Research
• [Presentation] Clinical impact of chronic total occlusion in non-infarct-related artery on long-term clinical outcomes in patients with multi-vessel disease undergoing primary PCI for ST-elevation acute myocardial infarction (from the CREDO-Kyoto AMIregistry). (2015)
  • Author(s): Watanabe H, Shiomi H, Kimura T.
  • Organizer: ESC CONGRESS 2015
  • Place of Presentation: London（UK）
  • Year and Date: 2015-08-29 – 2015-09-02
  • Int'l Joint Research
• [Presentation] Short versus prolonged dual antiplatelet therapy (DAPT) duration after coronary stent implantation: a comparison between the DAPT trial and 9 other trials evaluating DAPT duration. (2015)
  • Author(s): Toyota T, Shiomi H, Morimoto T, Natsuaki M, Kimura T.
  • Organizer: ESC CONGRESS 2015
  • Place of Presentation: London（UK）
  • Year and Date: 2015-08-29 – 2015-09-02
  • Int'l Joint Research
• [Presentation] DES 留置後の至適 DAPT 施行期間についての考察 (2015)
  • Author(s): 木村 剛
  • Organizer: 第79回 日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場外（大阪市）
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] 大規模レジストリ―の将来展望 CREDO-Kyoto Registry (2015)
  • Author(s): 木村 剛
  • Organizer: 第79回 日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場外（大阪市）
  • Year and Date: 2015-04-24 – 2015-04-26
• [Remarks] 京都大学医学部附属病院 循環器内科
  • URL: http://kyoto-u-cardio.jp/