Metabolic factors reflecting thrombogenicity of atherosclerotic plaque

• Project/Area Number: 25460440
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: University of Miyazaki
• Principal Investigator: Yamashita Atsushi 宮崎大学, 医学部, 助教 (90372797)
• Co-Investigator(Kenkyū-buntansha): MORIGUCHI SAYAKA 宮崎大学, 医学部, 助教 (90468041)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 動脈硬化性血栓 / プラークの血栓能 / 代謝 / 低酸素

Outline of Final Research Achievements

Atherosclerotic plaque disruption does not always result in acute symptomatic events. Therefore, the thrombogenicity of the atherosclerotic plaques is a critical factor in the development of atherothrombosis. However, little is known about determinants of the plaque thrombogenicity. We found that metabolite levels of glycolysis increase in macrophage-rich atherosclerotic arteries, and that arterial glucose uptake reflects vascular thrombogenicity, which might be partly explained by metabolic adaptation and enhanced procoagulant activity in a hypoxic microenvironment. Expression of hexokinase II, a glycolytic enxyme upregulated by hypoxia, in the atherosclerotic plaques correlated with human coronary thrombus size. The novel findings will allow the detection of high-risk plaques and the development of atherosclerosis therapies.

Research Products

• [Journal Article] Vascular wall hypoxia promotes arterial thrombus formation via augmentation of vascular thrombogenicity (2015)
  • Author(s): 2.Matsuura Y, Yamashita A, Iwakiri T, Sugita C, Okuyama N, Kitamura K, Asada Y.
  • Journal Title: Thromb Haemost. Volume: 114 Issue: 07 Pages: 158-172
  • DOI: 10.1160/th14-09-0794
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Human Coronary Thrombus Formation Is Associated With Degree of Plaque Disruption and Expression of Tissue Factor and Hexokinase II (2015)
  • Author(s): 6.Okuyama N, Matsuda S, Yamashita A, Moriguchi-Goto S, Sameshima N, Iwakiri T, Matsuura Y, Sato Y, Asada Y.
  • Journal Title: Circulation Journal Volume: 79 Issue: 11 Pages: 2430-2438
  • DOI: 10.1253/circj.CJ-15-0394
  • NAID: 130005104878
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Magnetic resonance imaging for qualitative assessment of deep vein thrombosis. (2015)
  • Author(s): Kuroiwa Y, Yamashita A, Imamura T, Asada Y.
  • Journal Title: Med Imag & Info Sci. Volume: 32 Pages: 100-102
  • NAID: 130005116569
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Values of Wall Shear Stress, Turbulence Kinetic Energy and Blood Pressure Gradient are Associated with Atherosclerotic Plaque Erosion in Rabbits (2014)
  • Author(s): Sameshima N, Yamashita A, Sato S, Matsuda S, Matsuura Y, Asada Y.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 21 Issue: 8 Pages: 831-838
  • DOI: 10.5551/jat.23093
  • NAID: 130004444797
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A synthetic tryptophan metabolite reduces hemorrhagic area and inflammation after pulmonary radiofrequency ablation in rabbit nonneoplastic lungs. (2014)
  • Author(s): Nakada H, Yamashita A, Kuroki M, Furukoji E, Uchino N, Asanuma T, Asada Y, Tamura S.
  • Journal Title: Jpn J Radiol Volume: 32 Issue: 3 Pages: 145-54
  • DOI: 10.1007/s11604-014-0282-4
  • NAID: 50009030776
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage (2014)
  • Author(s): Atsushi Yamashita, Yan Zhao, Yunosuke Matsuura, Kazuaki Yamasaki, Sayaka Moriguchi-Goto, Chihiro Sugita, Takashi Iwakiri, Nozomi Okuyama, Chihiro Koshimoto, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yuji Kuge, Yujiro Asada
  • Journal Title: PLos One Volume: 9 Issue: 1 Pages: e86426-e86426
  • DOI: 10.1371/journal.pone.0086426
  • Peer Reviewed / Open Access
• [Journal Article] Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor. (2013)
  • Author(s): Sugita C, Yamashita A, Matsuura Y, Iwakiri T, Okuyama N, Matsuda S, Matsumoto T, Inoue O, Harada A, Kitazawa T, Hattori K, Shima M, Asada Y.
  • Journal Title: Thromb Haemost Volume: 110 Issue: 07 Pages: 62-75
  • DOI: 10.1160/th13-01-0069
  • Peer Reviewed
• [Journal Article] Validation of a newly proposed histopathological classification in Japanese patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. (2013)
  • Author(s): Iwakiri T, Fujimoto S, Kitagawa K, Furuichi K, Yamahana J, Matsuura Y, Yamashita A, Uezono S, Shimao Y, Hisanaga S, Tokura T, Wada T, Kitamura K, Asada Y
  • Journal Title: BMC Nephrol. Volume: 14 Pages: 125-125
  • Peer Reviewed
• [Journal Article] Arterial (18)F-fluorodeoxyglucose uptake reflects balloon catheter-induced thrombus formation and tissue factor expression via nuclear factor-κB in rabbit atherosclerotic lesions. (2013)
  • Author(s): Yamashita A, Zhao Y, Zhao S, Matsuura Y, Sugita C, Iwakiri T, Okuyama N, Ohe K, Koshimoto C, Kawai K, Tamaki N, Kuge Y, Asada Y.
  • Journal Title: Circ J Volume: 77 Pages: 2626-35
  • Peer Reviewed
• [Journal Article] Association between renal vasculature changes and generalized atherosclerosis: an autopsy survey. (2013)
  • Author(s): Iwakiri T, Sato Y, Matsuura Y, Hatakeyama K, Marutsuka K, Yamashita A, Fujimoto S, Kitamura K, Asada Y.
  • Journal Title: J Atheroscler Thromb Volume: 21 Pages: 99-107
  • NAID: 130004444703
  • Peer Reviewed
• [Presentation] Vascular wall hypoxia promotes arterial thrombus formation. (2015)
  • Author(s): Yamashita A, Matsuura Y, Asada Y
  • Organizer: The 3rd Conference of the Japanese Association for hypoxia biology
  • Place of Presentation: Tokyo
  • Year and Date: 2015-07-25
  • Int'l Joint Research
• [Presentation] Pathological determinants of human coronary thrombus formation: distinct procoagulant activity and lactate production of M1/M2 polarized macrophages. (2015)
  • Author(s): Matsuda S, Yamashita A, Moriguchi-Goto S, Sameshima N, Iwakiri T, Yunosuke Matsuura Y, Sato Y, Asada Y
  • Organizer: XXV Congress, International Socitety on Thrombosis and Haemostasis
  • Place of Presentation: Toronto
  • Year and Date: 2015-06-20
  • Int'l Joint Research
• [Presentation] 冠動脈の血栓サイズに関連する血管性因子：解糖系代謝と凝固活性の関連 (2015)
  • Author(s): 山下 篤、盛口清香、佐藤勇一郎、浅田祐士郎
  • Organizer: 第37回日本血栓止血学会学術集会
  • Place of Presentation: 甲府
  • Year and Date: 2015-05-21
  • Int'l Joint Research
• [Presentation] Determinants of coronary thrombogenicity: Distinct tissue factor activity and lactate production in M1/M2 polarized macrophages. (2015)
  • Author(s): Yamashita A, Asada Y.
  • Organizer: IXth Aso International Meeting
  • Place of Presentation: Aso
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] 動脈硬化血管及びマクロファージの代謝状態と低酸素の影響 (2014)
  • Author(s): 山下 篤、趙 芫、松浦祐之介、山崎一諒、盛口清香、越本知大、川井 恵一、趙 松吉、久下裕司、浅田祐士郎
  • Organizer: 第36回日本血栓止血学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-05-29 – 2014-05-31
• [Presentation] ウサギ動脈硬化血管の代謝解析と血栓能の評価 (2014)
  • Author(s): 山下 篤
  • Organizer: 第36回日本血栓止血学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-05-29 – 2014-05-31
  • Invited
• [Presentation] Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage. (2014)
  • Author(s): Yamashita A, Zhao Y, Matsuura Y, Yamasaki K, Moriguchi-Goto S, Sugita C, Iwakiri T, Okuyama N, Koshimoto C, Kawai K, Tamaki N, Zhao S, Kuge Y, Asada Y.
  • Organizer: Arteriosclerosis, Thrombosis and Vascular Biology 2014, Scientific Sessions
  • Place of Presentation: Toronto
  • Year and Date: 2014-05-01 – 2014-05-03
• [Presentation] 動脈硬化巣の低酸素は血栓形成を促進する (2013)
  • Author(s): 山下 篤、松浦祐之介、杉田千泰、岩切太幹志、奥山 希、浅田祐士郎
  • Organizer: 第35回日本血栓止血学会学術集会
  • Place of Presentation: 山形市
• [Presentation] 冠動脈血栓においてプラーク破綻の大きさと組織因子発現の程度は血栓サイズと相関する (2013)
  • Author(s): 松田俊太郎、奥山 希、山下 篤、盛口清香、佐藤勇一郎、畠山金太、丸塚浩助、浅田祐士郎
  • Organizer: 第35回日本血栓止血学会学術集会
  • Place of Presentation: 山形市
• [Presentation] Metabolic changes in rabbit atherosclerotic arteries: Increased glucose uptake and metabolite levels of glycolysis, pentose phosphate pathway, tricarboxylic acid cycle and nucleotides. (2013)
  • Author(s): Atsushi Yamashita, Yan Zhao, Yunosuke Matsuura, Kazuaki Yamasaki, Chihiro Sugita, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yuji Kuge, Yujiro Asada
  • Organizer: XXIVth congress of the international society on thrombosis and haemostasis
  • Place of Presentation: Amsterdam
• [Presentation] Human coronary thrombus formation is associated with degree of plaque disruption and expression of tissue factor and hexokinase II in atherosclerotic plaques (2013)
  • Author(s): Shuntaro Matsuda, Nozomi Okuyama, Atsushi Yamashita, Sayaka Moriguchi, Yuichiro Sato, Kinta Hatakeyama, Kousuke Marutsuka, Yujiro Asada
  • Organizer: XXIVth congress of the international society on thrombosis and haemostasis
  • Place of Presentation: Amsterdam
• [Presentation] Elevated plasma level of factor VIII enhances venous thrombus fromation and propagation in rabbit: Contribution of thrombin, factor XI, von Willebrand factor, and tissue factor (2013)
  • Author(s): Chihiro Sugita, Atsushi Yamashita, Yunosuke Matsuura, Takashi Iwakiri, Nozomi Okuyama, Shuntaro Matsuda, Tomoko Matsumoto, Osamu Inoue, Aya Harada, Takehisa Kitazawa, Kunihiro Hattori, Midori Shima, Yujiro Asada
  • Organizer: XXIVth congress of the international society on thrombosis and haemostasis
  • Place of Presentation: Amsterdam
• [Book] Thrombosis, atherosclerosis and atherothrombosis: New insights and experimental protocols (2015)
  • Author(s): Yamashita A, Asada Y
  • Total Pages: 141
  • Publisher: Intech