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

2011 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

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測定で検討した。心臓再同期療法を行った心不全患者において治療後に有意な血管内皮機能改善を認めた。左心室収縮の保たれた心不全患者(HFNEF)においてRH-PAT測定で評価した血管内皮機能は将来の心血管イベント発症の有意な独立した危険因子であることが明らかとなった。虚血性心疾患疑いの患者においては、冠動脈造影検査で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臨床背景の特徴として痩せた閉経後女性で非発作時に境界領域の虚血性心電図変化を示し、非発作時冠動脈血流パターンに特徴があることが明らかとなった。心嚢脂肪蓄積が左心室拡張障害存在の独立した危険因子になること、冠動脈プラーク全体容積の評価を64列心臓CT検査で評価しMetabolic Syndromeの存在で有意に冠動脈プラーク量増大が確認された。スタチンと運動療法の併用による介入研究でアロルバスタチンに比べてロスバスタチンによって有意なHDL上昇効果が確認された。新たな糖尿病治療薬であるDPP-IV阻害剤による治療で動脈硬化モデルであるApoE欠損マウスにおいてSitagliptinは有意に動脈硬化行変形成を抑制することが明らかとなった

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

研究結果の集計と統計解析は完了し、今年は論文作成と発表の段階となっており順調な経過と考えられる。

Strategy for Future Research Activity

臨床研究において心血管イベント発生を検討するために予後調査を行う。
順調に研究は遂行できており問題点や変更点はない。

Research Products

• [Journal Article] A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoproteln E-deficient mice (2012)
  • Author(s): Matsubara J, Sugiyama S, Sugamura K, Nakamura T, Fujiwara Y, Akiyama E, Kurokawa H, Nozaki T, Ohba K, Konishi M, Maeda H, Izumiya Y, Kaikita K, Sumida H, Jinnouchi H, Matsui K, Kim-Mitsuyama S, Takeya M, Ogawa H
  • Journal Title: Journal of the American College of Cardiology Volume: 59 Pages: 265-276
  • DOI: PMID:22240132[PubMed-indexed for MEDLINE]
  • Peer Reviewed
• [Journal Article] Accumulation of pericardial fat correlates with left ventricular diastolic dysfunction in patients with normal ejection fraction (2012)
  • Author(s): Konishi M, Sugiyama S, Sugamura K, Nozaki T, Matsubara J, Akiyama E, Utsunomiya D, Matsuzawa Y, Yamashita Y, Kimura K, Umemura S, Ogawa H
  • Journal Title: Journal of Cardiology Volume: (Epub)(印刷中)
  • DOI: PMID:22365950[PubMed-as supplied by publisher]
  • Peer Reviewed
• [Journal Article] Low-dose contrast protocol using the test bolus technique for 64-detector computed tomography coronary angiography (2012)
  • Author(s): Nakaura T, Awai K, Yanaga Y, Namimoto T, Utsunomiya D, Hirai T, Sugiyama S, Ogawa H, Aoyama M, Yamashita Y
  • Journal Title: Jpn J Radiol Volume: 29 Pages: 457-465
  • DOI: PMID:21882087[PubMed-indexed for MEDLINE]
  • Peer Reviewed
• [Journal Article] Total coronary artery plaque burden measured by cardiac computed tomography is associated with metabolic syndrome (2011)
  • Author(s): Konishi M, Sugiyama S, Sugamura K, Nozaki T, Ohba K, Matsubara J, Sumida H, Nagayoshi Y, Utsunomiya D, Awai K, Yamashita Y, Matsuzawa Y, Kimura K, Umemura S, Ogawa H
  • Journal Title: J Atheroscler Thromb Volume: 18 Pages: 939-945
  • DOI: PMID:21785228[PubMed-indexed for MEDLINE]
  • Peer Reviewed
• [Journal Article] Improvement effect on endothelial function in patients with congestive heart failure treated with cardiac resynchronization therapy (2011)
  • Author(s): Enomoto K, Yamabe H, Toyama K, Matsuzawa Y, Yamamuro M, Uemura T, Morihisa K, Iwashita S, Kaikita K, Sugiyama S, Ogawa H
  • Journal Title: Journal of Cardiology Volume: 58 Pages: 69-73
  • DOI: PMID:21493043[PubMed-indexed for MEDLINE]
  • Peer Reviewed
• [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: 217 Pages: 158-164
  • DOI: PMID:21458815[PubMed-indexed for MEDLINE]
  • Peer Reviewed
• [Presentation] Incremental Significance of Endothelial Function Assessed by Reactive Hyperemia Peripheral Arterial Tonometry for Predicting Cardiovascular Events in stable Patients With Coronary Artery Disease (2012)
  • Author(s): Matsuzawa Y, Sugiyama S, Akiyatna E, Umemura S, Kimura K, Ogawa H
  • Organizer: American College of Cardiology 2012
  • Place of Presentation: Chicago McCormick Place
  • Year and Date: 2012-03-26
• [Presentation] <シンポジウム>Heart Failure with Preserved Ejection Fraction Incremental Prognostic Significance of Peripheral Endothelial Dysfunction in Patients with Heart Failure with Normal Left Ventricular Ejection Fraction (2012)
  • Author(s): Akiyama E, Ohba K, Sugiyama S, Konishi M, Nozaki T, Matsubara J, Sumida H, Matsui K, Kimura K, Umemura S, Ogawa H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡福岡国際会議場
  • Year and Date: 2012-03-18
• [Presentation] Asian Joint Case-Conference 10 : Thailand and Japan Effects of Immediate Statin-therapy on Left Ventricular Remodeling and Functions after STelevated Myocardial Infarction Treated by Coronary Stenting (2012)
  • Author(s): Seigo Sugiyama, Tadasuke Chitose, Hideki Shimomura, Takuro Yamashita,Jun Hokamaki, Ryusuke Tsunoda, Hisao Ogawa
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡福岡国際会議場(招待講演)
  • Year and Date: 2012-03-18
• [Presentation] Clinical Significance and Characteristic of Coronary Microvascular Spasm in Non-Obstructive Coronary Artery Disease (2012)
  • Author(s): Ohba K, Sugiyama S, Matsubara J, Maeda H, Kurokawa H, Ogawa H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡福岡国際会議場
  • Year and Date: 2012-03-18
• [Presentation] <シンポジウム>冠狭窄病変のない狭心症へのアプローチComprehensive Diagnostic Approach to Non-obstructive Coronary Artery Disease by Using Coronary Doppler FloWire and EndoPAT2000-Role of Endothelial Dysfunction- (2012)
  • Author(s): Sugiyama S, Matsuzawa Y, Ohba K, Ogawa H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡マリンメッセ福岡
  • Year and Date: 2012-03-17
• [Presentation] <シンポジウム>心血管リスク評価におけるイメージングと生理機能検査の意義Incremental Significance of Endothelial Function Assessed by Peripheral Arterial Tonometry for Predicting Cardiovascular Events in Patients with Coronary Artery Disease (2012)
  • Author(s): Matsuzawa Y, Sugiyama S, Sumida H, Nozaki T, Sugamura K, Matsubara J, Ohba K, Konishi M, Akiyama E, Suzuki H, Iwashita S, Matsui K, Kimura K, Umemura S, Ogawa H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡福岡サンパレス
  • Year and Date: 2012-03-17
• [Presentation] モーニングレクチャー:拡張不全と炎症Inflammation and Endothelial Dysfunction in Heart Failure Patients with Preserved Left Ventricular Ejection Fraction (HFpEF) (2012)
  • Author(s): Seigo Sugiyama, Junichi Matsubara, Eiichi Akiyama, Yasushi Matsuzawa, Kazuo Kimura, Hisao Ogawa
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡福岡国際会議場(招待講演)
  • Year and Date: 2012-03-17
• [Presentation] Dipeptidyl Peptidase-4 Inhibitor, Des-Fluoro-Sitagliptin, Improved Endothelial Function through Enhancing Action of Glucagon-like Peptide-1 in Vivo and in Vitro (2012)
  • Author(s): Matsubara J, Sugiyama S, Nakamura T, Kurokawa H, Iwashita S, Ohba K, Maeda H, Jinnouchi H, Kim- Mitsuyama S, Ogawa H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡福岡国際センター
  • Year and Date: 2012-03-16
• [Presentation] Beneficial Myocardial Effects of Immediate Rosuvastatin-therapy on Left Ventricular Remodeling and Functions after ST-elevated Myocardial Infarction Treated by Coronary Stenting (2012)
  • Author(s): Chitose T, Sugiyama S, Shimomura H, Yamashita T, Hokamaki J, Tsunoda R, Ogawa H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡マリンメッセ福岡
  • Year and Date: 2012-03-16
• [Presentation] Decreased Plasma Levels of Active Glucagon-Like Peptide-1 Correlate with Coronary Artery Disease and Coronary Plaque Complexity in High-risk Patients (2012)
  • Author(s): Akiyama E, Sugiyama S, Konishi M, Ohba K, Nozaki T, Matsubara J, Sumida H, Kimura K, Umemura S, Ogawa H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡マリンメッセ福岡
  • Year and Date: 2012-03-16
• [Presentation] Combined Treatment with Dipeptidyl-Peptidase-4 Inhibitor and Glucagon-like Peptide-1 Attenuated Endothelium Inflammation through Activation of AMP-activated Protein Kinase/Endothelial-Nitric Oxide Synthase Pathway (2012)
  • Author(s): Kurokawa H, Sugiyama S, Matsubara J, Ohba K, Maeda H, Ogawa H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡福岡サンパレス
  • Year and Date: 2012-03-16
• [Presentation] <シンポジウム>Cardiovascular Risk Stratification of by Endothelium-Derived Microparticles (2011)
  • Author(s): Sugiyama S, Nozaki T, Koga H, Ogawa H
  • Organizer: The 19^<th> Annual Meeting of the Japanese Vascular Biology and Medicine Organization/The 1^<st> Asia-Pacific Vascular Biology Meeting
  • Place of Presentation: 東京Tokyo Station Conference(招待講演)
  • Year and Date: 2011-12-09
• [Presentation] Incremental Prognostic Significance of Peripheral Endothelial Dysfunction for Cardiovascular Events in Patients with Heart Failure with Normal Left Ventricular Ejection Fraction (2011)
  • Author(s): Akiyama E, Sugiyama S, Matsuzawa Y, Konishi M, Nozaki T, Ohba K, Matsubara J, Sugamura K, Sumida H, Kaikita K, Iwashita S, Matsui K, Kimura K, Umemura S, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, Florida Orange County Convention Center
  • Year and Date: 2011-11-16
• [Presentation] Peripheral Endothelial Dysfunction is a Significant Determinant of Contrast-Induced Renal Damage in Patients Underwent Percutaneous Coronary Procedures (2011)
  • Author(s): Sumida H, Matsuzawa Y, Sugiyama S, Akiyama E, Iwashita S, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, Florida Orange County Convention Center
  • Year and Date: 2011-11-15
• [Presentation] Utility of Digital Assessment of Endothelial Function for Cardiovascular Risk Stratification in Patients with Diabetes Mellitus (2011)
  • Author(s): Matsuzawa Y, Sugiyama S, Hitoshi S, Sugamura K, Nozaki T, Ohba K, Konishi M, Matsubara J, Akiyama E, Iwashita S, Matsui K, Umemura S, Kimura K, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, Florida Orange County Convention Center
  • Year and Date: 2011-11-15
• [Presentation] Decreased Plasma Levels of Active Glucagon-Like Peptide-1 Correlate With Coronary Artery Disease and Coronary Plaque Complexity in High-Risk Patients (2011)
  • Author(s): Akiyama E, Sugiyama S, Matsuzawa Y, Konishi M, Nozaki T, Ohba K, Matsubara J, Sumida H, Kaikita K, Kimura K, Umemura S, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, Florida Orange County Convention Center
  • Year and Date: 2011-11-15
• [Presentation] Dipeptidyl Peptidase-4 Inhibitor, Des-Fluoro-Sitagliptin, Improved Endothelial Function through Enhancing Action of Glucagon-Like Peptide-1 in vivo and in vitro (2011)
  • Author(s): Matsubara J, Sugiyama S, Nakamura T, Kurokawa H, Ohba K, Maeda H, Shokei Kim-Mitsuyama, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, Florida Orange County Convention Center
  • Year and Date: 2011-11-14
• [Presentation] Beneficial Myocardial Effects of Immediate Rosuvastatin-Therapy on Left Ventricular Functions after ST-Elevated Myocardial Infarction (2011)
  • Author(s): Chitose T, Sugiyama S, Shimomura H, Yamashita T, Hokamaki J, Tsunoda R, Shiraishi S, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, Florida Orange County Convention Center
  • Year and Date: 2011-11-14
• [Presentation] Digital Assessment of Peripheral Endothelial Function for the Risk Stratification in Patients With Hypertension (2011)
  • Author(s): Matsuzawa Y, Sugiyama S, Sumida H, Sugamura K, Nozaki T, Ohba K, Konishi M, Matsubara J, Akiyama E, Iwashita S, Matsui K, Umemura S, Kimura K, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, Florida Orange County Convention Center
  • Year and Date: 2011-11-13
• [Presentation] Increased Oxidative Stress in Heart Failure With Normal Left Ventricular Ejection Fraction (2011)
  • Author(s): Akiyama E, Sugiyama S, Matsuzawa Y, Konishi M, Nozaki T, Ohba K, Matsubara J, Sumida H, Kaikita K, Kimura K, Umemura S, Ogawa H
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando, Florida Orange County Convention Center
  • Year and Date: 2011-11-13
• [Presentation] <シンポジウム>新しい炎症マーカーであるPentraxin3と拡張障害、拡張障害性心不全との関係 (2011)
  • Author(s): 杉山正悟、松原純一、小川久雄
  • Organizer: 第15回日本心不全学会学術集会
  • Place of Presentation: 鹿児島かごしま県民交流センター(招待講演)
  • Year and Date: 2011-10-13
• [Presentation] Endothelial Dysfunction is a Significant Determinant Factor of Contrast-Induced Renal Dysfunction in Patients with Early stage of Chronic Kidney Disease<プレナリーセッション> (2011)
  • Author(s): Sumida H, Sugiyama S, Matsuzawa Y, Nozaki T, Akiyama E, Matsubara J, Tsujita K, Kaikita K, Ohba K, Konishi M, Yamamuro M, Izumiya Y, Kojima S, Hokimoto S, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] <シンポジウム>心臓CTとMRIの最前線Cardiac Computed Tomography Assessment of Pericardial Fat Associated with Coronary Atherosclerosis and Left Ventricular Diastolic Dysfunction (2011)
  • Author(s): Konishi M, Sugiyama S, Nozaki T, Ohba K, Akiyama E, Sakamoto K, Sumida H, Kimura K, Umemura S, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] Increased Levels of Average Peak Velocity of Coronary Flow at Baseline Condition Associates with Non-obstructive Coronary Artery Disease (2011)
  • Author(s): Ohba K, Sugiyama S, Sumida H, Nozaki T, Akiyama E, Matsubara J, Ono T, Yamamoto K, Morihisa K, Yamamoto Y, Tsujita K, Nagayoshi Y, Yamamuro M, Izumiya Y, Kojima S, Kaikita K, Hokimoto S, Tayama S, Koyama J, Yamabe H, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] Increased Oxidative stress in Heart Failure with Normal Left Ventricular Ejection Fraction (2011)
  • Author(s): Akiyama E, Sugiyama S, Konishi M, Ohba K, Nozaki T, Matsubara J, Sumida H, Kimura K, Umemura s, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] Decreased Plasma Levels of Glucagon-Like Peptide-1 Associate with Coronary Artery Disease in High Risk Patients (2011)
  • Author(s): Akiyama E, Sugiyama S, Konishi M, Ohba K, Nozaki T, Matsubara J, Sumida H, Kimura K, Umemura S, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] Digital Assessment of Endothelial Dysfunction in Patients with Coexistence of Coronary Artery Disease and Peripheral Arterial Disease-Effects of Cilostazol- (2011)
  • Author(s): Maeda H, Matsuzawa Y, Sumida H, Sugiyama S, Ogawa H, Jinnouchi H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] Utility of Digital Assessment of Endothelial Function for Cardiovascular Risk Stratification in Patients with Diabetes Mellitus (2011)
  • Author(s): Matsuzawa Y, Sugiyama S, Kimura K, Umemura S, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] Dipeptidyl Peptidase-4 Inhibitor Improved Endothelial Function and Reduced Atherosclerotic Lesion Formation in Apolipoprotein E-deficient Mice (2011)
  • Author(s): Matsubara J, Sugiyama S, Sugamura K, Nozaki T, Nakamura T, Ohba K, Akiyama E, Maeda F, Izumiya Y, Kaikita K, Sumida H, Shokei Kim-Mitsuyama, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] Decreased Diastolic to Systolic Velocity Ratio of Basal Coronary Artery Flow Associates with Coronary Microvascular Spasm in Normal Coronary Angiography (2011)
  • Author(s): Ohba K, Sugiyama S, Sumida H, Nozaki T, Akiyama E, Matsubara J, Ono T, Yamamoto K, Morihisa K, Yamamoto E, Tsujita K, Nagayoshi Y, Yamamuro M, Izumiya Y, Kojima S, Kaikita K, Hokimoto S, Tayama S, Koyama J, Yamabe H, Ogawa H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-08-03
• [Presentation] 冠動脈疾患患者におけるRosuvastatin服用下の長期運動は、CoenzymeQ10をさげることなくHDL-Cを有意にに上昇する (2011)
  • Author(s): 外山研介, 杉山正悟, 岡秀樹, 濱田真理, 里田亜矢子, 小川久雄
  • Organizer: 第17回心臓リハビリテーション学会学術集会YIA
  • Place of Presentation: 大阪大阪国際会議場(YIA優秀賞を受賞)
  • Year and Date: 2011-07-16
• [Presentation] Rosuvastatin服用下の長期運動は、冠動脈疾患患者の血中CoenzymeQ10を維持したままHDL-Cを増加させる (2011)
  • Author(s): 外山研介, 杉山正悟, 岡秀樹, 角田等, 田中朋子, 田山信至, 陣内秀昭, 小川久雄
  • Organizer: 第110回日本循環器学会九州地方会:YIA
  • Place of Presentation: 福岡アクロス福岡(YIA最優秀賞を受賞)
  • Year and Date: 2011-06-25
• [Presentation] <シンポジウム>ガス分子による血管内皮機能調節～血管内皮機能測定の意義と問題点～血管内皮機能と心血管リスク (2011)
  • Author(s): 杉山正悟、松澤泰志、秋山英一、小川久雄
  • Organizer: 第11回日本NO学会学術集会
  • Place of Presentation: 東京昭和薬科大学(招待講演)
  • Year and Date: 2011-05-14