Clinical Assessment of Endothelial Dysfunction and Investigationof New Therapies in Cardiovascular Diseases

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590786
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: SUGIYAMA Seigo 熊本大学, 大学院・生命科学研究部, 准教授 (90274711)
• Project Period (FY): 2010 – 2012
• Keywords: 臨床心血管病態学 / 血管内皮細胞障害 / 冠動脈疾患 / 心不全 / 心血管イベント / 危険因子 / 動脈硬化

Research Abstract

We examined Reactive Hyperemia Peripheral Arterial Tonometry(RH-PAT) test and measurement of plasma levels of Endothelium-derived Microparticles(EMP) in patients suspected with coronary artery disease and heart failure patients inorder to assess vascular endothelial dysfunction clinically. We found CD144-EMP was anindependent prognostic factor for cardiovascular events in patients with heart failurewith reduced LVEF. We demonstrated the presence of coronary endothelial dysfunction andidentified distinctive clinical features in patients with coronary microvascular spasticangina. The vascular endothelial function assessed by RH-PAT test in patients with heartfailure with normal LVEF (HFNEF) was a significant and independent factor of the futurecardiovascular events. We demonstrated that the treatment by DPP-IV inhibitor(Sitagliptin); a new medicine for diabetes, improved the vascular endothelial functionand significantly inhibited atherosclerosis formation in the ApoE deficiency mouse, amouse model of atherosclerosis.

Research Products

• [Journal Article] Basal andischemia-induced transcardiac troponinrelease into the coronary circulationin patients with suspected coronaryartery disease (2013)
  • Author(s): Konishi M, Sugiyama S, Sugamura K,Nozaki T, Ohba K, Matsubara J, SakamotoK, Nagayoshi Y, Sumida H, Akiyama E,Matsuzawa Y, Sakamaki K, Morita S,Kimura K, Umemura S, Ogawa H
  • Journal Title: PLoS One Volume: 8(4) Pages: e60163
  • DOI: DOI:10.1371/journal.pone.0060163
  • Peer Reviewed
• [Journal Article] Dipeptidyl Peptidase-4 Inhibitor,Sitagliptin, Improves EndothelialDysfunction in Association With ItsAnti-Inflammatory Effects in PatientsWith Coronary Artery Disease andUncontrolled Diabetes (2013)
  • Author(s): Matsubara J, Sugiyama S, Akiyama E,Iwashita S, Kurokawa H, Ohba K, Maeda H,Fujisue K, Yamamoto E, Kaikita K,Hokimoto S, Jinnouchi H, Ogawa H
  • Journal Title: Circ J Volume: 77 Pages: 1337-1344
  • DOI: DOI:10.1253/circ.CJ-12-1168
  • Peer Reviewed
• [Journal Article] Microvascular coronary artery spasmpresents distinctive clinical featureswith endothelial dysfunction asnonobstructive coronary artery disease (2012)
  • Author(s): Ohba K, Sugiyama S, Sumida H, Nozaki T, Matsubara J, Matsuzawa Y, Konishi M, Akiyama E, Kurokawa H, Maeda H, Sugamura K, Nagayoshi Y, Morihisa K, Sakamoto K, Tsujita K, Yamamoto E, Yamamuro M, Kojima S, Kaikita K, Tayama S, Hokimoto S, Matsui K, Sakamoto T, Ogawa H
  • Journal Title: J Am Heart Assoc Volume: 1(5) Pages: e002485
  • DOI: DOI:10.1161/JAHA.112.002485
  • Peer Reviewed
• [Journal Article] Incremental prognostic significance ofperipheral endothelial dysfunction inpatients with heart failure with normalleft ventricular ejection fraction (2012)
  • Author(s): Akiyama E, Sugiyama S, Matsuzawa Y,Konishi M, Suzuki H, Nozaki T, Ohba K,Matsubara J, Maeda H, Horibata Y,Sakamoto K, Sugamura K, Yamamuro M,Sumida H, Kaikita K, Iwashita S, MatsuiK, Kimura K, Umemura S, Ogawa H
  • Journal Title: JAm Coll Cardiol Volume: 60(18) Pages: 1778-86
  • DOI: DOI:10.1016/j.jacc.2012.07.036
  • Peer Reviewed
• [Journal Article] Combination treatment ofrosuvastatin or atorvastatin, withregular exercise improves arterial wallstiffness in patients with coronaryartery disease (2012)
  • Author(s): Toyama K, Sugiyama S, Oka H, Iwasaki Y,Sumida H, Tanaka T, Tayama S, JinnouchiH, Ogawa H
  • Journal Title: PLoS One Volume: 7(7) Pages: e41369
  • DOI: DOI:10.1371/journal.pone.0041369
  • Peer Reviewed
• [Journal Article] Accumulation of pericardial fatcorrelates with left ventriculardiastolic dysfunction in patients withnormal 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: J Cardiol Volume: 59(3) Pages: 344-51
  • DOI: DOI:10.1016/j.jjcc.2012.01.006
  • Peer Reviewed
• [Journal Article] A dipeptidylpeptidase-4 inhibitor,des-fluoro-sitagliptin, improvesendothelial function and reducesatherosclerotic lesion formation inapolipoprotein 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: J AmColl Cardiol Volume: 59(3) Pages: 265-76
  • DOI: DOI:10.1016/j.jacc.2011.07.053
  • Peer Reviewed
• [Journal Article] Total coronaryartery plaque burden measured bycardiac computed tomography isassociated 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: JAtheroscler Thromb Volume: 18(11) Pages: 939-45
  • Peer Reviewed
• [Journal Article] Improvement effect on endothelialfunction in patients with congestiveheart failure treated with cardiacresynchronization therapy (2011)
  • Author(s): Enomoto K, Yamabe H, Toyama K, MatsuzawaY, Yamamuro M, Uemura T, Morihisa K,Iwashita S, Kaikita K, Sugiyama S, OgawaH
  • Journal Title: J Cardiol Volume: 58(1) Pages: 69-73
  • DOI: DOI:10.1016/j.jjcc.2011.01.010
  • Peer Reviewed
• [Journal Article] Rosuvastatincombined with regular exercisepreserves coenzyme Q10 levelsassociated with a significant increase in high-density lipoproteincholesterol in patients with coronaryartery disease (2011)
  • Author(s): Toyama K, Sugiyama S, Oka H, Iwasaki Y,Sumida H, Tanaka T, Tayama S, JinnouchiH, Matsui K, Ogawa H
  • Journal Title: Atherosclerosis Volume: 217(1) Pages: 158-64
  • DOI: DOI:10.1016/j.atherosclerosis.2011.02.050
  • Peer Reviewed
• [Journal Article] Pentraxin 3 isa new inflammatory marker correlatedwith left ventricular diastolicdysfunction and heart failure withnormal ejection fraction (2011)
  • Author(s): Matsubara J, Sugiyama S, Nozaki T,Sugamura K, Konishi M, Ohba K, MatsuzawaY, Akiyama E, Yamamoto E, Sakamoto K,Nagayoshi Y, Kaikita K, Sumida H,Kim-Mitsuyama S, Ogawa H
  • Journal Title: J Am CollCardiol Volume: 57(7) Pages: 861-9
  • DOI: DOI:10.1016/j.jacc.2010.10.018
  • Peer Reviewed
• [Journal Article] Pericardial fat inflammationcorrelates with coronary artery disease (2010)
  • Author(s): Konishi M, Sugiyama S, Sato Y, Oshima S,Sugamura K, Nozaki T, Ohba K, MatsubaraJ, 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(2) Pages: 649-55
  • DOI: DOI:10.1016/j.atherosclerosis.2010.10.007
  • Peer Reviewed
• [Journal Article] Prognostic value ofendothelial microparticles in patientswith heart failure (2010)
  • Author(s): Nozaki T, Sugiyama S, Sugamura K, OhbaK, Matsuzawa Y, Konishi M, Matsubara J,Akiyama E, Sumida H, Matsui K, JinnouchiH, Ogawa H
  • Journal Title: Eur J Heart Fail Volume: 12(11) Pages: 1223-8
  • DOI: DOI:10.1093/eurjhf/hfq145
  • Peer Reviewed
• [Journal Article] Exercise therapy correlateswith improving renal function throughmodifying lipid metabolism in patientswith cardiovascular disease and chronickidney disease (2010)
  • Author(s): Toyama K, Sugiyama S, Oka H, Sumida H,Ogawa H
  • Journal Title: J Cardiol Volume: 56(2) Pages: 142-6
  • DOI: DOI:10.1016/j.jjcc.2010.06.007
  • Peer Reviewed
• [Journal Article] Digitalassessment of endothelial function andischemic heart disease in women (2010)
  • Author(s): Matsuzawa Y, Sugiyama S, Sugamura K,Nozaki T, Ohba K, Konishi M, MatsubaraJ, Sumida H, Kaikita K, Kojima S,Nagayoshi Y, Yamamuro M, Izumiya Y,Iwashita S, Matsui K, Jinnouchi H,Kimura K, Umemura S, Ogawa H
  • Journal Title: J AmColl Cardiol Volume: 55(16) Pages: 1688-96
  • DOI: DOI:10.1016/j.jacc.2009.10.073
  • Peer Reviewed
• [Journal Article] Association of pericardial fataccumulation rather than abdominalobesity with coronary atheroscleroticplaque formation in patients withsuspected coronary artery disease (2010)
  • Author(s): Konishi M, Sugiyama S, Sugamura K、Nozaki T, Ohba K, Matsubara J, MatsuzawaY, Sumida H, Nagayoshi Y, Nakaura T,Awai K, Yamashita Y, Jinnouchi H, MatsuiK, Kimura K, Umemura S, Ogawa H
  • Journal Title: Atherosclerosis Volume: 209(2) Pages: 573-8
  • DOI: DOI:10.1016/j.atherosclerosis.2009.10.008.
  • Peer Reviewed
• [Presentation] How to Reduce Residual Riskin Patients with DM in the Statin Era? (2013)
  • Author(s): 杉山 正悟
  • Organizer: 第77回日本循環器学会学術集会(招待講演)
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2013-03-19
• [Presentation] 血管内皮機能検査から全身を診る 「血管内皮機能検査による心血管リスクの評価の実際と臨床応用 (2012)
  • Author(s): 杉山 正悟
  • Organizer: 第60回日本心臓病学会学術集会 (招待講演)
  • Place of Presentation: ホテル日航金沢、金沢市
  • Year and Date: 2012-09-16
• [Presentation] 血管病変の非侵襲的評価法の有用性 (2012)
  • Author(s): 杉山 正悟
  • Organizer: 第60回日本心臓病学会学術集会 (招待講演)
  • Place of Presentation: ホテル日航金沢、 金沢市
  • Year and Date: 2012-09-14
• [Presentation] 拡張不全と炎症 (2012)
  • Author(s): 杉山 正悟
  • Organizer: 第76回日本循環器学会学術集会(招待講演)
  • Place of Presentation: 福岡 福岡国際会議場
  • Year and Date: 2012-03-17
• [Presentation] 新しい炎症マーカーである Pentraxin3 と拡張障害 (2011)
  • Author(s): 杉山 正悟
  • Organizer: 拡張障害性心不全との関係 第15回日本心不全学会学術集会(招待講演)
  • Place of Presentation: 鹿児島 かごしま県民交流センター
  • Year and Date: 2011-10-13
• [Presentation] 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 (2011)
  • Author(s): 杉山 正悟
  • Organizer: 第11回日本NO学会学術集会(招待講演)
  • Place of Presentation: 東京 昭和薬科大学
  • Year and Date: 2011-05-14