Promotion of Plaque Stability by Glucagon-like Peptide-1 Receptor Agonist: Serial In Vivo Findings

• Project/Area Number: 25461094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nihon University
• Principal Investigator: HIRAYAMA Atsushi 日本大学, 医学部, 教授 (50459880)
• Co-Investigator(Kenkyū-buntansha): HIRO Takafumi 日本大学, 医学部, 教授 (10294638) ; MITSUMATA Masako 日本大学, 医学部, 兼任講師 (40064589)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 動脈硬化 / インクレチン / GLP-1受容体作動薬

Outline of Final Research Achievements

We investigated the effects of glucagon-like peptide-1(GLP-1)on atherosclerotic plaque in Watanabe heritable hyperlipidemic (WHHL) rabbit. The WHHL rabbits were divided into GLP-1 group or control group. GLP-1 receptor agonist was administered by osmotic pump in GLP-1 group. Same volume of normal saline was administered in control group. Atherosclerotic plaques inbrachiocephalic arteries were evaluated in vivo by Intravascular Ultrasound (IVUS) before and 12 weeks after GLP-1 receptor agonist treatment. Finally, the arteries were harvested and the atherosclerotic plaques were evaluated with pathological analysis.In comparison to control group, IVUS analysis revealed that GLP-1 receptor agonist inhibited plaque development with less plaque growth and increased plaque stability. Pathological analysis confirmed the IVUS findings with increased fibrotic content. Our study suggested that GLP-1 receptor agonist may stabilize atherosclerotic plaque.

Research Products

• [Journal Article] The Spatial Distribution of Plaque Vulnerabilities in Patients with Acute Myocardial Infarction. (2016)
  • Author(s): Zheng G, Li Y, Takayama T, Nishida T, Sudo M, Haruta H, Fukamachi D, Okubo K, Higuchi Y, Hiro T, Saito S, Hirayama A.
  • Journal Title: PLoS One Volume: 11 Issue: 3 Pages: e0152825-e0152825
  • DOI: 10.1371/journal.pone.0152825
  • Peer Reviewed
• [Journal Article] Comparison of the Effect of Rosuvastatin 2.5 mg vs 20 mg on Coronary Plaque Determined by Angioscopy and Intravascular Ultrasound in Japanese With Stable Angina Pectoris (from the Aggressive Lipid-Lowering Treatment Approach Using Intensive Rosuvastatin for Vulnerable Coronary Artery Plaque [ALTAIR] Randomized Trial). (2016)
  • Author(s): Takayama T, Komatsu S, Ueda Y, Fukushima S, Hiro T, Hirayama A, Saito S; ALTAIR study group
  • Journal Title: Am J Cardiol Volume: 117 Pages: 1206-1212
  • Peer Reviewed
• [Journal Article] The Effect of Statin Therapy on Coronary Plaque Composition Using Virtual Histology Intravascular Ultrasound: A Meta-Analysis. (2015)
  • Author(s): Zheng G, Li Y, Huang H, Wang J, Hirayama A, Lin J.
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0133433-e0133433
  • DOI: 10.1371/journal.pone.0133433
  • Peer Reviewed
• [Journal Article] Tissue characteristics of non-culprit plaque in patients with acute coronary syndrome vs. stable angina: a color-coded intravascular ultrasound study. (2015)
  • Author(s): Sudo M, Hiro T, Takayama T, Iida K, Nishida T, Fukamachi D, Kawano T, Higuchi Y, Hirayama A.
  • Journal Title: Cardiol Volume: 66 Issue: 5 Pages: 388-394
  • DOI: 10.1016/j.jjcc.2015.06.006
  • NAID: 40020699729
  • Peer Reviewed
• [Journal Article] Early detection of vulnerable atherosclerotic plaque for risk reduction of acute aortic rupture and thromboemboli and atheroemboli using non-obstructive angioscopy. (2015)
  • Author(s): Komatsu S, Ohara T, Takahashi S, Takewa M, Minamiguchi H, Imai A, Kobayashi Y, Iwa N, Yutani C, Hirayama A, Kodama K.
  • Journal Title: Circ J Volume: 79 Issue: 1 Pages: 742-750
  • DOI: 10.1186/s12959-015-0035-3
  • NAID: 130005130233
  • Peer Reviewed
• [Journal Article] Association between the Epicardial Adipose Tissue Thickness and the Presence of Multivessel Disease in Patients with Acute Myocardial Infarction (2015)
  • Author(s): Fukamachi D, Higuchi Y, Hiro T, Takayama T, Kanai T, Sudo M, Nishida T, Iida K, Saito S, Hirayama A.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 22 Issue: 2 Pages: 144-151
  • DOI: 10.5551/jat.26120
  • NAID: 130004687429
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Effects of the T/L-type Calcium Channel Blocker Benidipine on Albuminuria and Plasma Aldosterone Concentration. (2014)
  • Author(s): Tani S, Takahashi A, Nagao K, Hirayama A.
  • Journal Title: Int Heart J. Volume: 55 Pages: 519-525
  • Peer Reviewed
• [Journal Article] Impact of Coronary Plaque Burden and Composition on Periprocedural Myocardial Infarction and Coronary Flow Reserve After Percutaneous Coronary Intervention. (2014)
  • Author(s): Higuchi Y, Hiro T, Takayama T, Kanai T, Kawano T, Fukamachi D, Sudo M, Nishida T, Iida K, Saito S, Hirayama A.
  • Journal Title: Int Heart J. Volume: 55 Pages: 391-396
  • NAID: 130004678090
  • Peer Reviewed
• [Journal Article] Effects of Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, in Hypercholesterolemic, Statin-Treated Japanese Patients at High Cardiovascular Risk (2014)
  • Author(s): Hirayama A, Honarpour N, Yoshida M, Yamashita S, Huang F, Wasserman SM, Teramoto T
  • Journal Title: Circ J Volume: 78 Pages: 1073-1082
• [Journal Article] Multi-modality visualization with three-dimensional reconstruction of neointimal plaque rupture after bare metal stent implantation. (2014)
  • Author(s): Mitsumasa Sudo, Takafumi Hiro, Tadateru Takayama, Korehito Iida, Naotaka Akutsu, Toshihiko Nishida, Takashi Kanai, Taro Kawano, Yoshiharu Higuchi, Atsushi Hirayama
  • Journal Title: Journal of the American College of Cardiology;Cardiovascular Intervetion Volume: ７ Issue: 10 Pages: e163-e165
  • DOI: 10.1016/j.jcin.2014.04.023
  • Peer Reviewed / Open Access
• [Journal Article] Plaque stabilization by intensive LDL-cholesterol lowering therapy with atorvastatin is delayed in type 2 diabetic patients with coronary artery disease-Serial angioscopic and intravascular ultrasound analysis (2013)
  • Author(s): T. Takayama, T. Hiro, Y. Ueda, J. Honye, S. Komatsu, O. Yamaguchi, Y. Li, J. Yajima, K. Takazawa, S. Nanto, S. Saito , A. Hirayama and K. Kodama
  • Journal Title: J. Cardiol Volume: 61 Issue: 6 Pages: 381-386
  • DOI: 10.1016/j.jjcc.2013.01.010
  • Peer Reviewed
• [Journal Article] Miglitol improves postprandial endothelial dysfunction in patients with acute coronary syndrome and new-onset postprandial hyperglycemia. (2013)
  • Author(s): Kitano D, Chiku M, Li Y, Okumura Y, Fukamachi D, Takayama T, Hiro T, Saito S, Hirayama A.
  • Journal Title: Cardiovasc Diabetol Volume: 12 Issue: 1 Pages: 92-92
  • DOI: 10.1186/1475-2840-12-92
  • Peer Reviewed
• [Presentation] Plaque Spatial Distribution of the Sites of Potential Vulnerability of Culprit Lesions Implicated in Acute Myocardial Infarction (2016)
  • Author(s): Guian Zheng ,Tadateru Takayama、Yuxin Li、Yoshiharu Higuchi、Daisuke Fukamachi、Hironori Haruta、Mitsumasa Sudo、Toshihiko Nishida、Satoshi Saito、Takafumi Hiro、Atsushi Hirayama
  • 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（宮城・仙台）
  • Year and Date: 2016-03-18
• [Presentation] Different Roles of sdLDL Cholesterol and HDL Cholesterol Subfractions in Predicting Plaque Burden and Composition of Coronary Culprit Lesions (2016)
  • Author(s): Y Li ,A Onishi、T Takayama、M Sudo、S Suzuki、D Fuchimoto、S Sembon、M Iwamoto、M Hashimoto、S Kunimoto、T Hiro、T Matsumoto、M Mitsumata、M Sugitani、S Saito、A Hirayama
  • 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（宮城・仙台）
  • Year and Date: 2016-03-18
• [Presentation] 光干渉断層撮影法を用いた冠動脈内新生血管(micro channel;MC)の検出と血管内視鏡によるその臨床的意義の検討 (2015)
  • Author(s): 西田 俊彦, 廣 高史, 高山 忠輝, 飯田 維人, 須藤 晃正, 春田 裕典, 深町 大介, 川野 太郎, 奥村 恭男, 金井 孝司, 樋口 義治, 齋藤 頴, 平山 篤志
  • Organizer: 第６３回日本心臓病学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川・横浜）
  • Year and Date: 2015-09-18
• [Presentation] 家畜ブタを用いた薬剤溶出性ステント留置後リバロキサバンによる抗血栓効果および新生内膜修復効果の検討 (2015)
  • Author(s): 須藤 晃正, 廣 高史, 高山 忠輝, 三俣 昌子, 平山 篤志
  • Organizer: 第６３回日本心臓病学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川・横浜）
  • Year and Date: 2015-09-18
• [Presentation] 遺伝性高コレステロール血症ウサギWHHL-MIにおけるHMG-CoA還元酵素阻害薬ピタバスタチンによる動脈硬化性プラーク進展抑制のメカニズム (2015)
  • Author(s): 春田 裕典, 廣 高史, 須藤 晃正, 深町 大介, 西田 俊彦, 李 よきん, 平山 篤志, 高山 忠輝
  • Organizer: 第６３回日本心臓病学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川・横浜）
  • Year and Date: 2015-09-18
• [Presentation] Modification of plaque composition and improvement of plaque stability by glucagon-like peptide-1 (2014)
  • Author(s): 須藤 晃正
  • Organizer: ESC2014
  • Place of Presentation: バルセロナ（スペイン）
  • Year and Date: 2014-09-02
• [Presentation] Ameliorative effect of glucagon-like peptide-1 agonist, lixisenatide, on brachiocephalic atherosclerosis in Watanabe Heritableanalysis. Hyperlipidemic rabbits: IVUS and pathologic (2014)
  • Author(s): 須藤 晃正
  • Organizer: 第23回日本心血管インターベンション治療学会
  • Place of Presentation: 名古屋国際会議場（愛知県、名古屋市）
  • Year and Date: 2014-07-24
• [Presentation] Association between Epicardial Adipose Tissue and Development of Pan-coronary Atherosclerosis in Patients with Acute Coronary Syndrome (2014)
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: 第78 回 日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Comparison of Mid-term Thrombogenicity of Everolimus-versus Paclitaxel-eluting Stents with the Same Stent Platform: A Coronary Angioscopic Study (2014)
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: 第78 回 日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Scar Size and Characteristics Assessed by 2D and 3D Gadolinium-enhanced MRI Imaging Predict the Inducibility and Origin of Ventricular Arrhythmias (2014)
  • Author(s): 平山篤志
  • Organizer: 第７８回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Identification of Multiple Biomarkers That Predict the Extent of Plaque Burden in Coronary Culprit Lesions (2014)
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: 第７８回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] ３Dプラークイメージングからみた急性冠症候群の発症機序 (2013)
  • Author(s): 廣 高史
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本
• [Presentation] 光干渉断層撮影法を用いた冠動脈内新生血管の検出とi-map softwareによるその臨床的意義の検討 (2013)
  • Author(s): 平山篤志 、 廣 高史
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本
• [Presentation] 2型糖尿病を合併した虚血性心疾患患者に対するDPP-4阻害薬、アログリプチンの臨床的効果の検討 (2013)
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本
• [Presentation] STEMI患者におけるEESステント留置後の血管内視鏡による観察 (2013)
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本
• [Presentation] 冠動脈ステント留置時におけるプラーク量とプラーク性状が冠微小循環障害に与える影響 (2013)
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本
• [Presentation] 冠動脈疾患の至適薬物治療 冠動脈プラークの経時的変化からみた至適薬物療法としてのスタチンの効果 血管内超音波、血管内視鏡による検討 (2013)
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本
• [Presentation] Angioscopic prevalence in diabetic patients with everolimus-eluting stent compared to paclitaxel-eluting stent,a serial observation of coronary angioscopy in multicenter.
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: ESC
  • Place of Presentation: Netherlands
• [Presentation] Comparison of mid-term thrombogenicity of everolimus-versus paclitaxel-eluting stents stents with the same stent platform.:acoronary angioscopic study.
  • Author(s): 平山 篤志 、 廣 高史
  • Organizer: ESC
  • Place of Presentation: Netherlands
• [Presentation] Pleiotropic Effects of Statin in Stabilization of Unstable Coronary Plaque-Direct Evidence from Low Density Lipoprotein Receptor knockout Pig
  • Author(s): 平山 篤志
  • Organizer: AHA
  • Place of Presentation: アメリカ