three-dimensional structure building of neovascularization in coronary plaque: role of VEGF family

• Project/Area Number: 16K09479
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: Nishiguchi Tsuyoshi 和歌山県立医科大学, 医学部, 博士研究員 (40549771)
• Co-Investigator(Kenkyū-buntansha): 田中 篤 和歌山県立医科大学, 医学部, 准教授 (50458072) ; 樽谷 玲 和歌山県立医科大学, 医学部, 博士研究員 (60612942)
• Project Period (FY): 2016-04-01 – 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 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 急性冠症候群 / 光干渉断層法 OCT / プラークの不安定化 / VEGF / プラーク不安定化 / 冠動脈疾患 / 新生血管 / プラーク破裂 / 炎症 / 光干渉断層法 / 血管新生 / 循環器・高血圧

Outline of Final Research Achievements

The research focus of our group is to elucidate the pathogenesis of coronary plaques and acute coronary syndromes. We examined coronary plaques in patients with coronary artery disease with optical coherence tomography in vivo. We found that serum MMP-9 level in coronary circulation were elevated in acute myocardial infarction. We also reported that higher levels of VEGF receptor 1 in coronary circulation are associated with greater neovascular volume in the plaque in patient with acute myocardial infarction. Furthermore, we reported that cholesterol crystals in the coronary plaque was associated with coronary plaque rupture and the onset of myocardial infarction.

Academic Significance and Societal Importance of the Research Achievements

急性心筋梗塞は突然死や心不全の原因であり、本邦だけでなく世界的にも、克服すべき大きな課題である。我々は光干渉断層法を用いて、ヒト生体内で冠動脈プラークを評価することに大きな強みを持っている。今回我々は、光干渉断層法を応用し、これまで評価困難であった、ヒト生体内のプラーク内新生血管やプラーク内のコレステロールクリスタルについて報告した。冠動脈内新生血管やコレステロールクリスタルは、新たな研究や治療のターゲットになる可能性があり、本研究はその基礎となるものである。

Research Products

• [Journal Article] Lesion characteristics and prognosis of acute coronary syndrome without angiographically significant coronary artery stenosis. (2020)
  • Author(s): Taruya A, Tanaka A, Nishiguchi T, Ozaki Y, Kashiwagi M, Yamano T, Matsuo Y, Ino Y, Kitabata H, Takemoto K, Kubo T, Hozumi T, Akasaka T.
  • Journal Title: Eur Heart J Cardiovasc Imaging. Volume: 21(2) Pages: 202-209
  • DOI: 10.1093/ehjci/jez079
  • Peer Reviewed
• [Journal Article] Feasibility and Clinical Significance of In Vivo Cholesterol Crystal Detection Using Optical Coherence Tomography. (2020)
  • Author(s): Katayama Y, Tanaka A, Taruya A, Kashiwagi M, Nishiguchi T, Ozaki Y, Matsuo Y, Kitabata H, Kubo T, Shimada E, Kondo T, Akasaka T.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 40(1) Issue: 1 Pages: 220-229
  • DOI: 10.1161/atvbaha.119.312934
  • Peer Reviewed / Open Access
• [Journal Article] Combination of Lesion Stenosis and Myocardial Supply Area Assessed by Coronary Computed Tomography Angiography for Prediction of Myocardial Ischemia (2019)
  • Author(s): Manabu Kashiwagi
  • Journal Title: International Heart Journal Volume: 60 Issue: 6 Pages: 1238-1244
  • DOI: 10.1536/ihj.19-141
  • NAID: 130007753839
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2019-11-30
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic Value of Human Peripheral Monocyte Subsets for Future Coronary Events in Patients Without Significant Coronary Artery Stenosis (2019)
  • Author(s): Prognostic Value of Human Peripheral Monocyte Subsets for Future Coronary Events in Patients Without Significant Coronary Artery Stenosis
  • Journal Title: Circulation Journal Volume: 83 Issue: 11 Pages: 2250-2256
  • DOI: 10.1253/circj.CJ-19-0520
  • NAID: 130007733355
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-10-25
  • Peer Reviewed / Open Access
• [Journal Article] Association of Hemodynamic Severity With Plaque Vulnerability and Complexity of Coronary Artery Stenosis: A Combined Optical Coherence Tomography and Fractional Flow Reserve Study. (2019)
  • Author(s): Matsuo Y, Higashioka D, Ino Y, Shiono Y, Kitabata H, Terada K, Emori H, Katayama Y, Taruya A, Nishiguchi T, Shimamura K, Kameyama T, Kuroi A, Yamano T, Tanimoto T, Tanaka A, Hozumi T, Kubo T, Akasaka T.
  • Journal Title: JACC. Cardiovascular imaging Volume: 12 Issue: 6 Pages: 1103-1105
  • DOI: 10.1016/j.jcmg.2018.11.023
  • Peer Reviewed
• [Journal Article] Imaging assessment and accuracy in coronary artery autopsy: comparison of frequency-domain optical coherence tomography with intravascular ultrasound and histology (2019)
  • Author(s): Aiko Shimokado, Takashi Kubo, Yoshiki Matsuo, Yasushi Ino, Yasutsugu Shiono, Kunihiro Shimamura, Yosuke Katayama, Akira Taruya, Tsuyoshi Nishiguchi, Manabu Kashiwagi, Hironori Kitabata, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
  • Journal Title: The International Journal of Cardiovascular Imaging Volume: 35 Pages: 1785-1790
  • Peer Reviewed
• [Journal Article] Toll‐Like Receptor 9 Plays a Pivotal Role in Angiotensin II Induced Atherosclerosis (2019)
  • Author(s): Fukuda Daiju、Nishimoto Sachiko、Aini Kunduziayi、Tanaka Atsushi、Nishiguchi Tsuyoshi et al.
  • Journal Title: Journal of the American Heart Association Volume: 8 Issue: 7
  • DOI: 10.1161/jaha.118.010860
  • NAID: 120006602927
  • Peer Reviewed / Open Access
• [Journal Article] In vivo optical coherence tomography imaging and histopathology of healed coronary plaques (2018)
  • Author(s): Shimokado Aiko、Matsuo Yoshiki、Kubo Takashi、Nishiguchi Tsuyoshi、Taruya Akira、Teraguchi Ikuko、Shiono Yasutsugu、Orii Makoto、Tanimoto Takashi、Yamano Takashi、Ino Yasushi、Hozumi Takeshi、Tanaka Atsushi、Muragaki Yasuteru、Akasaka Takashi
  • Journal Title: Atherosclerosis Volume: 275 Pages: 35-42
  • DOI: 10.1016/j.atherosclerosis.2018.05.025
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Early Pitavastatin Therapy on Coronary Fibrous-Cap Thickness Assessed by Optical Coherence Tomography in Patients With Acute Coronary Syndrome (2017)
  • Author(s): Nishiguchi Tsuyoshi、Kubo Takashi、Tanimoto Takashi、Ino Yasushi、Matsuo Yoshiki、Yamano Takashi、Terada Kosei、Emori Hiroki、Katayama Yosuke、Taruya Akira、Ozaki Yuichi、Shiono Yasutsugu、Shimamura Kunihiro、Kameyama Takeyoshi、Kitabata Hironori、Yamaguchi Tomoyuki、Tanaka Atsushi、Hozumi Takeshi、Akasaka Takashi
  • Journal Title: JACC Cardiovasc, Img. Volume: in press Issue: 6 Pages: 829-838
  • DOI: 10.1016/j.jcmg.2017.07.011
  • Peer Reviewed / Open Access
• [Journal Article] Automated lipid-rich plaque detection with short wavelength infra-red OCT system (2017)
  • Author(s): Shimokado Aiko、Kubo Takashi、Nishiguchi Tsuyoshi、Katayama Yosuke、Taruya Akira、Ohta Shingo、Kashiwagi Manabu、Shimamura Kunihiro、Kuroi Akio、Kameyama Takeyoshi、Shiono Yasutsugu、Yamano Takashi、Matsuo Yoshiki、Kitabata Hironori、Ino Yasushi、Hozumi Takeshi、Tanaka Atsushi、Akasaka Takashi
  • Journal Title: European Heart Journal Cardiovascular Imaging Volume: in press Issue: 10 Pages: 1174-1178
  • DOI: 10.1093/ehjci/jex304
  • Peer Reviewed / Open Access
• [Journal Article] Prognosis of spontaneous coronary artery dissection treated by percutaneous coronary intervention with optical coherence tomography (2017)
  • Author(s): Nishiguchi Tsuyoshi、Tanaka Atsushi、Taruya Akira、Ozaki Yuichi、Nakai Mai、Teraguchi Ikuko、Ota Shingo、Kuroi Akio、Kameyama Takeyoshi、Yamano Takashi、Yamaguchi Tomoyuki、Matsuo Yoshiki、Ino Yasushi、Kubo Takashi、Hozumi Takeshi、Akasaka Takashi
  • Journal Title: Jourl of Cardiology Volume: 70 Issue: 6 Pages: 524-529
  • DOI: 10.1016/j.jjcc.2017.03.009
  • Peer Reviewed / Open Access
• [Journal Article] Prognosis of Spontaneous Coronary Artery Dissection Treated by Percutaneous Coronary Intervention with Optical Coherence Tomography (2017)
  • Author(s): T Nishiguchi, A Tanaka, A Taruya, et al.
  • Journal Title: Journal of Cardiology Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Local matrix metalloproteinase 9 level determines early clinical presentation of ST-segment-elevation myocardial infarction. (2016)
  • Author(s): Tsuyoshi Nishiguchi, Atsushi Tanaka, Akira Taruya, Hiroki Emori, Yuichi Ozaki, Makoto Orii, Yasutsugu Shiono, Kunihiro Shimamura, Takeyoshi Kameyama, Takashi Yamano, Tomoyuki Yamaguchi, Yoshiki Matsuo, Yasushi Ino, Takashi Kubo, Takeshi Hozumi, Yasushi Hayashi, Takashi Akasaka
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 37 Issue: 12 Pages: 2460-2467
  • DOI: 10.1161/atvbaha.116.308099
  • Peer Reviewed
• [Presentation] Systemic Soluble VEGF-R1 as a Marker for Intraplaque Neovascularization in Patients With STEMI (2018)
  • Author(s): Akira Taruya , Atsushi Tanaka , Tsuyoshi Nishiguchi , Kazuya Mori , Shingo Ota , Takashi Tanimoto , and Takashi Akasaka
  • Organizer: アメリカ心臓病学会 2018
  • Int'l Joint Research
• [Presentation] Obesity, and low high-density lipoprotein are residual cardiovascular risks despite optimal low-density lipoprotein reduction with statins: a substudy of the ESCORT trial (2017)
  • Author(s): Nishiguchi T, Kubo T, Tanimoto T, et al.
  • Organizer: European Society of Cardiology 2017
  • Int'l Joint Research
• [Presentation] Lesion characteristics and prognosis of heart attack without obstructive coronary artery disease (2017)
  • Author(s): Taruya A, Tanaka A, Nishiguchi T, et al.
  • Organizer: European Society of Cardiology 2017
  • Int'l Joint Research
• [Presentation] Effect of early pitavastatin therapy on coronary fibrous-cap thickness assessed by optical coherence tomography in patients with acute coronary syndrome: the ESCORT study (2017)
  • Author(s): Nishiguchi T, Kubo T, Tanimoto T, et al.
  • Organizer: European Society of Cardiology 2017
  • Int'l Joint Research
• [Presentation] Association of Local Matrix Metalloproteinase 9 Levels with Clinical Manifestation in Patients with Acute Myocardial Infarction (2016)
  • Author(s): T Nishiguchi, A Tanaka, A Taruya, et al.
  • Organizer: European Society of Cardiology Congress 2016
  • Place of Presentation: ローマ、イタリア
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Effect of Early Statin Therapy on Fibrous-cap Thickness in Patients with Acute Coronary Syndrome: The ESCORT Study (2016)
  • Author(s): T Nishiguchi, T Kubo, Y Ino, et al.
  • Organizer: European Society of Cardiology Congress 2016
  • Place of Presentation: ローマ、イタリア
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Effect of Early Statin Therapy on Fibrous-cap Thickness in Patients with Acute Coronary Syndrome: The ESCORT Study (2016)
  • Author(s): T Nishiguchi, T Kubo, Y Ino, et al.
  • Organizer: Japanese Association of Cardiovascular Intervention and Therapeutics 2016
  • Place of Presentation: 東京
  • Year and Date: 2016-07-07