心血管疾患における血管内皮細胞障害の評価と新たな治療法の研究

2010 Fiscal Year Annual Research Report

• Project/Area Number: 22590786
• Research Institution: Kumamoto University
• Principal Investigator: 杉山 正悟 熊本大学, 大学院・生命科学研究部, 准教授 (90274711)
• Keywords: 臨床研究 / 循環器・高血圧 / 血管内皮 / ミトコンドリア / microparticles

Research Abstract

日本人心血管疾患患者とハイリスク患者における血管内皮細胞障害を臨床的に評価するために、冠動脈疾患疑い患者と心不全患者において、生理学的評価であるRH-PATと病理学的評価であるEMP測定で検討した。収縮不全心不全患者における血管内皮細胞機能障害をCD144-EMPにて評価し、その予後を検討したところ、EMPはBNPと共に独立した心血管イベント発症の予後規定因子であった。心不全の病態に慢性炎症の関与が示唆されているが、拡張不全心不全における炎症の関与は明らかではなかった。我々は新規炎症因子Pentmxin 3が、心不全発症前の拡張不全状態と拡張不全心不全において血中レベルで上昇すること、拡張不全状態や心不全状態の心臓から産生されていることを示した。拡張不全心不全の病態に炎症が重要な役割を果たしていることを臨床的に初めて示した。虚血性心疾患疑いの患者においては、冠動脈造影検査において有意な器質的狭窄を有さない患者で、多段階投与によるACh負荷試験を行いFloWireによる左冠動脈前下行枝近位部における冠動脈血流量測定と大動脈-冠静脈洞における乳酸測定を同時施行し(新たな冠動脈ACh負荷試験)冠動脈血管内皮細胞機能、冠微小循環、心筋虚血の評価を総合的に行った。その結果、冠微小血管攣縮性狭心症の診断法の確立と臨床特徴検討を行い、女性における非閉塞性冠動脈疾患の診断におけるRH-PAT検査の有用性を明らかにした。非閉塞性冠動脈疾患はFRSではその罹患リスク推定は全く出来ず、RH-PAT検査のみが有意な検出感度を示した。心嚢脂肪蓄積が冠動脈プラーク存在の独立した危険因子になること、心嚢脂肪炎症が冠動脈プラークの存在や急性冠症候群の病因・病態に関与する可能性が示された。運動療法による介入研究で腎機能に対する新たな効果とスタチンとの併用でHDL上昇に対する相乗効果を示した。

Research Products

• [Journal Article] Rosuvastatin combined with regular exercise preserves coenzyme Q10 levels associated with a significant increase in high-density lipoprotein cholesterol in patients with coronary artery disease. (2011)
  • Author(s): Toyama K, Sugiyama S, Oka H, Iwasaki Y, Sumida H, Tanaka T, Tayama S, Jinnouchi H, Matsui K, Ogawa H.
  • Journal Title: Atherosclerosis Volume: (Epub)
  • Peer Reviewed
• [Journal Article] Pentraxin 3 is a new inflammatory marker correlated with left ventricular diastolic dysfunction and heart failure with normal ejection fraction. (2011)
  • Author(s): Matsubara J, Sugiyama S, Nozaki T, Sugamura K, Konishi M, Ohba K, Matsuzawa Y, Akiyama E, Yamamoto E, Sakamoto K, Nagayoshi Y, Kaikita K, Sumida H, Kim-Mitsuyama S, Ogawa H.
  • Journal Title: J Am Coll Cardiol Volume: 57 Pages: 861-869
  • Peer Reviewed
• [Journal Article] Low-dose aspirin therapy in patients with type 2 diabetes and reduced glomerular filtration rate : subanalysis from the JPAD trial. (2011)
  • Author(s): Saito Y, Morimoto T, Ogawa H, Nakayama M, Uemura S, Doi N, Jinnouchi H, Waki M, Soejima H, Sugiyama S, Okada S, Akai Y ; Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes Trial Investigators.
  • Journal Title: Diabetes Care Volume: 34 Pages: 280-285
  • Peer Reviewed
• [Journal Article] Long-term use of oral nicorandil stabilizes coronary plaque in patients with stable angina pectoris. (2011)
  • Author(s): Izumiya Y, Kojima S, Kojima S, Araki S, Usuku H, Matsubara J, Sakamoto K, Tsujita K, Nagayoshi Y, Kaikita K, Sugiyama S, Ogawa H.
  • Journal Title: Atherosclerosis. Volume: 214 Pages: 415-421
  • Peer Reviewed
• [Journal Article] Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy. (2011)
  • Author(s): Yamamoto K, Hokimoto S, Chitose T, Morita K, Ono T, Kaikita K, Tsujita K, Abe T, Deguchi M, Miyagawa H, Saruwatari J, Sumida H, Sugiyama S, Nakagawa K, Ogawa H.
  • Journal Title: J Cardiol. Volume: 57 Pages: 194-201
  • Peer Reviewed
• [Journal Article] Hypercholesterolemia and hypoadiponectinemia are associated with necrotic core-rich coronary plaque. (2011)
  • Author(s): Kojima S, Kojima S, Maruyoshi H, Nagayoshi Y, Kaikita K, Sumida H, Sugiyama S, Funahashi T, Ogawa H.
  • Journal Title: Int J Cardiol. Volume: 147 Pages: 371-376
  • Peer Reviewed
• [Journal Article] Pericardial fat inflammation correlates with coronary artery disease. (2010)
  • Author(s): Konishi M, Sugiyama S, Sato Y, Oshima S, Sugamura K, Nozaki T, Ohba K, Matsubara J, Sumida H, Nagayoshi Y, Sakamoto K, Utsunomiya D, Awai K, Jinnouchi H, Matsuzawa Y, Yamashita Y, Asada Y, Kimura K, Umemura S, Ogawa H.
  • Journal Title: Atherosclerosis. Volume: 213 Pages: 649-655
  • Peer Reviewed
• [Journal Article] Impact of statin pretreatment on the incidence of plaque rupture in ST-elevation acute myocardial infarction. (2010)
  • Author(s): Otsuka F, Hibi K, Kusama I, Endo M, Kosuge M, Iwahashi N, Okuda J, Tsukahara K, Ebina T, Kojima S, Sugiyama S, Ogawa H, Umemura S, Kimura K.
  • Journal Title: Atherosclerosis Volume: 213 Pages: 505-511
  • Peer Reviewed
• [Journal Article] Prognostic value of endothelial microparticles in patients with heart failure. (2010)
  • Author(s): Nozaki T, Sugiyama S, Sugamura K, Ohba K, Matsuzawa Y, Konishi M, Matsubara J, Akiyama E, Sumida H, Matsui K, Jinnouchi H, Ogawa H.
  • Journal Title: Eur J Heart Fail. Volume: 12 Pages: 1223-1228
  • Peer Reviewed
• [Journal Article] Exercise therapy correlates with improving renal function through modifying lipid metabolism in patients with cardiovascular disease and chronic kidney disease. (2010)
  • Author(s): Toyama K, Sugiyama S, Oka H, Sumida H, Ogawa H.
  • Journal Title: J Cardiol. Volume: 56 Pages: 142-146
  • Peer Reviewed
• [Journal Article] Waveform of ophthalmic artery Doppler flow predicts the severity of systemic atherosclerosis. (2010)
  • Author(s): Maruyoshi H, Kojima S, Kojima S, Nagayoshi Y, Horibata Y, Kaikita K, Sugiyama S, Ogawa H.
  • Journal Title: Circ J. Volume: 74 Pages: 1251-1256
  • Peer Reviewed
• [Journal Article] Digital assessment of endothelial function and ischemic heart disease in women. (2010)
  • Author(s): Matsuzawa Y, Sugiyama S, Sugamura K, Nozaki T, Ohba K, Konishi M, Matsubara J, Sumida H, Kaikita K, Kojima S, Nagayoshi Y, Yamamuro M, Izumiya Y, Iwashita S, Matsui K, Jinnouchi H, Kimura K, Umemurn S, Ogawa H.
  • Journal Title: J Am Coll Cardiol. Volume: 74 Pages: 1251-1256
  • Peer Reviewed
• [Journal Article] Association of pericardial fat accumulation rather than abdominal obesity with coronary atherosclerotic plaque formation in patients with suspected coronary artery disease. (2010)
  • Author(s): Konishi M, Sugiyama S, Sugamura K, Nozaki T, Ohba K, Matsubara J, Matsuzawa Y, Sumida H, Nagayoshi Y, Nakaura T, Awai K, Yamashita Y, Jinnouchi H, Matsui K, Kimura K, Umemura S, Ogawa H.
  • Journal Title: Atherosclerosis. Volume: 209 Pages: 573-578
  • Peer Reviewed
• [Presentation] Dipeptidyl Peptidase-4 Inhibitor, Des-Fluoro-Sitagliptin (DFS), Improved Endothelial Function and Reduced Atherosclerotic Lesion Formation in Apolipoprotein E-deficient Mice (2010)
  • Author(s): J Matsubara, S Sugiyama, K Sugamura, T Nozaki, T Nakamura, K Ohba, E Akiyama, H Maeda, Y Izumiya, K Kaikita, H Sumida, S Kim-Mitsuyama, H Ogawa.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: McCORMICK PLACCE Chicago, Illinois, USA
  • Year and Date: 2010-11-17
• [Presentation] Accumulation of Pericardiol Fat Correlates with Diastolic Dysfunction in Patients with Preserved Ejection Fraction (2010)
  • Author(s): M Konishi, S Sugiyama, Y Matsuzawa, K Kimura, H Ogawa
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: McCORMICK PLACCE Chicago, Illinois, USA
  • Year and Date: 2010-11-17
• [Presentation] Diastolic to Systolic Velocity Ratio of Coronary Artery Flow at Basal Condition Indicates Coronary Microvessel Spasm in Normal Coronary Angiography. (2010)
  • Author(s): K Ohba, S Sugiyama, T Nozaki, E Akiyama, J Matsubara, H Maeda, H Sumida, S Takashio, H Kanazawa, T Chitose, K Enomoto, T Ono, K Yamamoto, E Yamamoto, T Tanaka, K Morihisa, K Tsujita, Y Nagayoshi, Y Izumiya, M Yamamuro, S Kojima, S Tayama, K Kaikita, S Hokimoto, H Yamabe, H Ogawa.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: McCORMICK PLACCE Chicago, Illinois, USA
  • Year and Date: 2010-11-17
• [Presentation] Efficacy of Low-dose Aspirin Therapy for Primary Prevention of Ath erosclerotic Events Depends on the Severity of Diabetes : a sub-analysis of JPAD trial. (2010)
  • Author(s): S Okada, T Morimoto, H Ogawa, M Nakayama, M Sakuma, S Uemura, M Kanauchi, N Doi, H Jinnouchi, H Soejima, S Sugiyama, M Waki, T Kawano, Y Saito
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: McCORMICK PLACCE Chicago, Illinois, USA
  • Year and Date: 2010-11-17
• [Presentation] Telmisartan Enhances Mitochondrial Biogenesis and Protects Endothelial Cells from Oxidative Injury Through AMP-Activated Protein Kinase. (2010)
  • Author(s): T Nozaki, S Sugiyama, K Sugamura, K Ohba, J Matsubara, E Akiyama, H Sumida, H Ogawa.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: McCORMICK PLACCE Chicago, Illinois, USA
  • Year and Date: 2010-11-16
• [Presentation] Functional CYP2C19 Gene Variants are Associated With Both On-clopidogrel Platelet Adhesiveness and Aggregation in Japanese Patients With Coronary Artery Disease (2010)
  • Author(s): K Kaikita, T Ono, S Hokimoto, K Tsujita, Y Miyazaki, K Sato, E Horio, H Sumida, S Sugiyama, H Ogawa.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: McCORMICK PLACCE Chicago, Illinois, USA
  • Year and Date: 2010-11-16
• [Presentation] Impact of Blood Pressure Control in Type 2 Diabetes Patients in Relation to Aspirin Therapy : Insight From the JPAD Trial. (2010)
  • Author(s): H Soejima, M Nakayama, T Morimoto, M Sakuma, S Uemura, M Kanauchi, N Doi, H Jinnouchi, S Sugiyama, M Waki, S Okada, T Kawano, Y Saito, H Ogawa
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: McCORMICK PLACCE Chicago, Illinois, USA
  • Year and Date: 2010-11-15
• [Presentation] Angiopoietin-Like Protein2 (angptl2) Promotes Coronary Endothelial Dysfunction and Atherosclerosis (2010)
  • Author(s): E Horio, K Kaikita, M Tabata, T Zhe, H Tazume, K Miyata, Y Miyazaki, T Ono, K Sato, K Tsujita, S Hokimoto, H Sumida, S Sugiyama, H Ogawa, Y Oike
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: McCORMICK PLACCE Chicago, Illinois, USA
  • Year and Date: 2010-11-15
• [Presentation] 非心臓血管手術周術期の心血管イベントおける病攣縮の影響 (2010)
  • Author(s): 永吉靖央, 角田等, 杉山正悟, 黒田豊, 海北幸一, 小川久雄
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム:東京
  • Year and Date: 2010-09-19
• [Presentation] たこつぼ型心筋症におけるST上昇と合併症の関係 (2010)
  • Author(s): 高潮征爾, 山室恵, 森久健二, 辻田賢一, 海北幸一, 掃本誠治, 角田等, 杉山正悟, 中尾浩一
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム:東京
  • Year and Date: 2010-09-19
• [Presentation] 持発性収縮性心膜炎に対して、ステロイド投与が著効した一例 (2010)
  • Author(s): 平田快絋, 森久健二, 坂本憲治, 辻田賢一, 海北幸一, 角田等, 杉山正悟, 小川久雄
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム:東京
  • Year and Date: 2010-09-19
• [Presentation] 拡張不全型心不全患者において酸化ストレスは進している-尿中8-hydroxy-2'-deoxyguanosine(8-OHdG)での検討 (2010)
  • Author(s): 秋山英一, 杉山正悟, 岩下さとみ, 木村一雄, 小川久雄
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム:東京
  • Year and Date: 2010-09-18
• [Presentation] 冠動脈疾患患者におけるチトクロームP4502C19遺伝子多型がクロピドグレルの血小板反応に与える影響 (2010)
  • Author(s): 山本浩一郎, 掃本誠治, 小野敬道, 辻田賢一, 海北幸一, 角田等, 杉山正悟, 中川和子
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム:東京
  • Year and Date: 2010-09-18
• [Presentation] 急性心筋梗塞患者における血清Flt3-Ligand濃度と末梢血樹状細胞数の減少 (2010)
  • Author(s): 福嶋隆一郎, 副島弘文, 福永崇, 杉山正悟, 小川久雄
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム:東京
  • Year and Date: 2010-09-18
• [Presentation] 待機的経皮的冠動脈インターベンション後の血中好感度トロポニンT濃度の上昇と寄与因子に関する検討 (2010)
  • Author(s): 小野敬道, 海北幸一, 佐藤幸治, 堀尾英治, 千年忠祐, 宮崎勇次, 辻田賢一, 坂本憲治, 田山信至, 掃本誠治, 角田等, 杉山正悟, 山部浩茂, 小川久雄
  • Organizer: 第58回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム:東京
  • Year and Date: 2010-09-17