Development of Diagnostic System of Vascular Function for Assessment of Atherosclerosis

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590898
• 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: Hiroshima University
• Principal Investigator: HIGASHI Yukihito 広島大学, 原爆放射線医科学研究所, 教授 (40346490)
• Co-Investigator(Kenkyū-buntansha): KIHARSA Yasuki 広島大学, 医歯薬学総合研究科, 教授 (40214853) ; TSUJI Toshio 広島大学, 工学研究院, 教授 (90179995)
• Project Period (FY): 2009 – 2011
• Keywords: 血管内皮機能 / 血管弾性 / バイオマーカー / 動脈硬化 / 血管状態測定装置

Research Abstract

We built a database for assessment of grade of atherosclerosis using measurement of endothelial function, including vascular unltrasound and plethysmography, measurement of arterial stiffness, including pulse-wave velocity and ankle-brachial pressure index, measurement of chemical biomarkers, and analysis of gene. In addition, we developed a new device for assessment of endothelial function. We are developing the analytic system software for diagnosis of grade of at herosclerosis.

Research Products

• [Journal Article] Geranylgeranylacetone, Hsp90/ AMPK/ eNOS/ NO pathway, and endothelial function in humans (2012)
  • Author(s): Fujimura N, Jitsuiki D, Goto C, Soga J, Hidaka T, Umemura T, Nishioka K, OshimaT, Chayama K, Higashi Y.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 153-160
  • Peer Reviewed
• [Journal Article] Xanthine oxidoreductase is involved inmacrophage foam cell formation and atherosclerosis development (2012)
  • Author(s): Kushiyama A, Zhang J, Sakoda H, KikuchiT, Fujishiro M, Sato H, Kushiyama S, Iwashita M, Nishimura F, Fukushima T, Nakatsu Y, Kamata, H, Kikuchi M, KawazuS, Higashi Y, Kurihara, H, Asano T.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 291-298
  • Peer Reviewed
• [Journal Article] Vascular dysfunction even after 20 years inchildren exposed to passive smoking : alarming results and need for awareness (2012)
  • Author(s): Suzuki T, Tomiyama H, Higashi Y.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 841-842
  • Peer Reviewed
• [Journal Article] Selective mineralocorticoid receptor blockere plerenone improves endothelialfunction and inhibits Rho-associatedkinase activity in patients with essential hypertension (2012)
  • Author(s): Fujimura N, Hata T, Soga J, Hidaka T, IdeiN, Fujii Y, Mikami S, Maruhashi T, Iwamoto Y, Kihara Y, Chayama K, Kato H, Noma K, Liao JK, Higashi Y.
  • Journal Title: Clin Pharmacol & Therapeut Volume: 91 Pages: 289-297
  • Peer Reviewed
• [Journal Article] A study design of multi-center study to evaluatethe clinical usefulness of semi-automatic measurement offlow-mediated vasodilatation of thebrachial artery in Japan(FMD-J study) (2012)
  • Author(s): Tomiyama H, Kohro T, Higashi Y, Takase B, Suzuki T, Ishizu T, Ueda S, Yamazaki T, Furumoto T, Kario K, Inoue T, Koba S, Watanabe K, Takemoto Y, Hano T, Sata M, Ishibashi Y, Node K, Maemura K, Ohya Y, Furukawa T, Ito H, Yamashina A.
  • Journal Title: Int Heart J. Volume: (in press)
  • Peer Reviewed
• [Journal Article] The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries (2012)
  • Author(s): Ohtsubo S, Ishikawa M, Kamei N, Kijima Y, Suzuki O, Sunagawa T, Higashi Y, MasudaH, Asahara T, Ochi M.
  • Journal Title: J Neurosurg Volume: (in press)
  • Peer Reviewed
• [Journal Article] Endothelial function and hypertension in aging(review) (2012)
  • Author(s): Higashi Y, Noma K.
  • Journal Title: Hypertens Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Strings of ROCK activity and endothelial function(review) (2012)
  • Author(s): Noma K, Kihara Y, Higashi Y.
  • Journal Title: J Cardiol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Vascular functionand circulating progenitor cell inthromboangiitis obliterans(Buergerdisease) and atherosclerosis obliterans (2011)
  • Author(s): Idei N, Nishioka K, Soga J, Hidaka T, HataT, Fujii Y, Fujimura N, Maruhashi T, Mikami S, Teragawa H, Kihara Y, Noma K, Chayama K, Higashi Y.
  • Journal Title: Hypertension Volume: 57 Pages: 70-78
  • Peer Reviewed
• [Journal Article] Autologous bone-marrow mononuclear cellimplantation reduces long-term majoramputation risk in patients withcritical limb ischemia : a comparison ofatherosclerotic peripheral arterialdisease and Buerger disease (2011)
  • Author(s): Idei N, Chowdhury M, Soga J, Hata T, FujiiY, Fujimura N, Mikami S, Maruhashi T, Nishioka K, Hidaka T, Kihara Y, Noma K, Taguchi A, Chayama K, Sueda T, Higashi Y.
  • Journal Title: Circulation : Cardiovascular Intervention Volume: 4 Pages: 15-25
  • Peer Reviewed
• [Journal Article] Response to Letter Regarding Article, Autologous bone-marrow mononuclear cellimplantation reduces long-term major amputation risk in patients withcritical limb ischemia : a comparison ofatherosclerotic peripheral arterialdisease and Buerger disease (2011)
  • Author(s): Idei N, Chowdhury M, Soga J, Hata T, FujiiY, Fujimura N, Mikami S, Maruhashi T, Nishioka K, Hidaka T, Kihara Y, Noma K, Taguchi A, Chayama K, Sueda T, Higashi Y.
  • Journal Title: Circulation : Cardiovascular Intervention Volume: 4 Pages: e13
  • Peer Reviewed
• [Journal Article] Calcium channel blockerand rho-associated kinae activity inpatients with hypertension (2011)
  • Author(s): Hata T, Soga J, Hidaka T, Idei N, FujiiY, Fujimura N, Mikami S, Maruhashi T, Kihara Y, Chayama K, Kato H, Noma K, LiaoJK, Higashi Y.
  • Journal Title: J Hypertens Volume: 29 Pages: 373-379
  • Peer Reviewed
• [Journal Article] Measurement of Rho-associatedkinase(ROCK) activity in humans : acomparison of leukocyte p-MBS/ t-MBS and forearm blood flow response to fasudil (2011)
  • Author(s): Hata T, Soga J, Hidaka T, Idei N, FujiiY, Fujimura N, Mikami S, Maruhashi T, Kihara Y, Chayama K, Noma K, Liao JK, Higashi Y.
  • Journal Title: Atherosclerosis Volume: 241 Pages: 117-121
  • Peer Reviewed
• [Journal Article] Rho-associated kinase(ROCK) activity, endothelial functionand cardiovascular risk factors (2011)
  • Author(s): Soga J, Hata T, Hidaka T, Fujii Y, IdeiN, Fujimura N, Mikami S, Maruhashi T, Kihara Y, Chayama K, Kato H, Noma K, LiaoJK, Higashi Y.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 31 Pages: 2353-2359
  • Peer Reviewed
• [Journal Article] Color Doppler flows of corkscrew collaterals in thromboangiitis obliterans(Buergerdisease) using color duplex ultrasonography (2011)
  • Author(s): Fujii Y, Soga J, Hidaka T, Hata T, IdeiN, Fujimura N, Mikami S, Maruhashi T, Noma K, Kihara Y, Higashi Y.
  • Journal Title: J Am Coll Cardiol Volume: 57 Pages: 2539
  • Peer Reviewed
• [Journal Article] Flow-mediated vasodilation is augmented in corkscrew collateral arterycompared with that in a native artery inpatients with thromboangiitis obliterans(Bureger disease) (2011)
  • Author(s): Fujii Y, Fujimura N, Mikami S, MaruhashiT, Kihara Y, Chayama K, Noma K, Higashi Y.
  • Journal Title: J Vas Surg Volume: 54 Pages: 546-547
  • Peer Reviewed
• [Journal Article] Is cell therapy promising orlost in translation in patients withacute myocardial infarction (2011)
  • Author(s): Higashi Y.
  • Journal Title: Circ J. Volume: 75 Pages: 546-547
  • Peer Reviewed
• [Journal Article] Relationship among hyperuricemia, metabolic syndrome, and endothelial dysfunction (2011)
  • Author(s): Tomiyama H, Higashi Y, Takase B, Node K, Sata M, Inoue T, Ishibashi Y, Ueda S, Yamashina A.
  • Journal Title: Am J Hypertens Volume: 24 Pages: 770-774
  • Peer Reviewed
• [Journal Article] Sarpogrelate, aselective 5-HT_<2A> antagonist, augments autologous bone-marrow mononuclear cellimplantation-induced improvement in endothelium-dependent vasodilation in patients with critical limb ischemia (2010)
  • Author(s): Higashi Y, Miyazaki M, Goto C, Sanada H, Chayama K, Sueda T.
  • Journal Title: J Cardiovasc Pharmacol Volume: 55 Pages: 56-61
  • Peer Reviewed
• [Journal Article] Increased leukocyte Rhokinase(ROCK) and endothelial dysfunction in cigarette smokers (2010)
  • Author(s): Hidaka T, Hata T, Soga J, Nakamura S, Fujii Y, Idei N, Fujimura N, Nishioka K, Kihara Y, Chayama K, Noma K, Liao JK, Higashi Y.
  • Journal Title: Hypertens Res Volume: 33 Pages: 354-359
  • Peer Reviewed
• [Journal Article] Pioglitazone improves endothelium-dependent vasodilation in hypertensive patients with impairedglucose tolerance through a decrease inoxidative stress (2010)
  • Author(s): Hidaka T, Nakagawa K, Goto C, Soga J, Fujii Y, Hata T, Idei N, Fujimura N, Chayama K, Kihara Y, Higashi Y.
  • Journal Title: Atherosclerosis Volume: 210 Pages: 521-524
  • Peer Reviewed
• [Journal Article] Endothelial function in subjects with isolated low HDL cholesterol : role of nitric oxide andcirculating progenitor cells (2010)
  • Author(s): Higashi Y, Matsuoka H, Umei H, Sugano R, Soga J, Fujii Y, Chayama K, Kihara Y, Imaizumi T.
  • Journal Title: Am J Physiol Endorinol Metab Volume: 298 Pages: E202-209
  • Peer Reviewed
• [Journal Article] Classification of corkscrew collateralsin thromboangiitis obliterans(Buerger' s disease): relationship between corkscrew type and prevalence of ischemic ulcers (2010)
  • Author(s): Fujii Y, Nishioka K, Nakamura S, HidakaT, Soga J, Hata T, Idei N, Fujimura N, Chayama K, Kihara Y, Higashi Y.
  • Journal Title: Circ J. Volume: 74 Pages: 1684-1688
  • Peer Reviewed
• [Journal Article] Anti-Aging Medicine in Cardiovascular Disease(review) (2010)
  • Author(s): Morishita R, Komuro I, Horiuchi M, Nakagami H, Minamino T, Higashi Y.
  • Journal Title: Anti-Aging Medicine Volume: 7 Pages: 45-49
  • Peer Reviewed
• [Journal Article] Impaired coronary microvascular endothelial function in men with metabolic syndrome (2010)
  • Author(s): Teragawa H, Mitsuba N, Nishioka K, UedaK, Kono S, Higashi Y, Chayama K, Kihara Y.
  • Journal Title: World J Cardiol Volume: 2 Pages: 205-210
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cellsenhance growth and metastasis of coloncancer (2010)
  • Author(s): Shinagawa K, Kitadai Y, Tanaka M, SumidaT, Kodama M, Higashi Y, Tanaka S, YasuiW, Chayama K.
  • Journal Title: Int J Cancer Volume: 127 Pages: 2323-2333
  • Peer Reviewed
• [Journal Article] on the behalf of the SEASON investigators. Study design of SEASON registry : prospective Surveillance of vascular Events in antiplatelet-treated Artero Sclerosis Obliterans patients inJapaN(SEASON) (2010)
  • Author(s): Higashi Y, Fujita M, Origasa H, NaritomiH, Matsuo H, Miyata T, Shigematsu H.
  • Journal Title: Int Heart J Volume: 51 Pages: 337-342
  • Peer Reviewed
• [Journal Article] Cigarette smoking abolished ischemic preconditioning-induced augmentation of endothelium-dependent vasodilation (2009)
  • Author(s): Nakamura S, Kimura M, Goto C, Kensuke N, Yoshizumi M, Chayama K, Kihara Y, Higashi Y.
  • Journal Title: Hypertension Volume: 53 Pages: 674-681
  • Peer Reviewed
• [Journal Article] Edaravone for Extending the therapeutic time window and rescue of ischemic penumbra in acute cerebralinfarction : role of endothelium-derivednitric oxide and oxidative stress(review) (2009)
  • Author(s): Higashi Y.
  • Journal Title: Expert Opin Pharmaco Volume: 10 Pages: 323-331
  • Peer Reviewed
• [Journal Article] Oxidative stress and endothelial function in cardiovascular diseases(review) (2009)
  • Author(s): Higashi Y, Noma K, Yoshizumi M, Kihara Y
  • Journal Title: Circ J. Volume: 73 Pages: 411-418
  • Peer Reviewed
• [Journal Article] Dietary Phosphorus Acutely Impairs Endothelial Function (2009)
  • Author(s): Shuto E, Taketani Y, Tanaka R, Harada N, Isshiki M, Sato M, Nashiki K, Amo K, Yamamoto H, Higashi Y, Nakaya N, Takeda E.
  • Journal Title: J Am Soc Nephrol Volume: 20 Pages: 1504-1512
  • Peer Reviewed
• [Journal Article] Oral infection-inflammatory pathway, periodontitis, is a risk factor for endothelial dysfunction in patients with coronary artery disease (2009)
  • Author(s): Higashi Y, Goto C, Hidaka T, Soga J, Nakamura S, Fujii Y, Hata T, Idei N, Fujimura N, Chayama K, Kihara Y, Taguchi A.
  • Journal Title: Atherosclerosis Volume: 206 Pages: 604-610
  • Peer Reviewed
• [Presentation] Assessment for Endothelial Function : Flow-mediated vasodilation(FMD) (2012)
  • Author(s): Yukihito Higashi
  • Organizer: 第76回日本循環器学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-17
• [Presentation] Rho-Associated Kinase(ROCK) Activity and Left Ventricular Hypertrophy in Patients with Essential Hypertension (2011)
  • Author(s): Shinsuke Mikami, Yukihito Higashi, Yuichi Fujii, Naomi Idei, Noritaka Fujimura, Takayuki Hidaka, Tatsuya Maruhashi, Yumiko Iwamoto, Yasuki Kihara
  • Organizer: 80^<th> Scientific Sessions, American Heart Association
  • Place of Presentation: Orlando, FA. USA
  • Year and Date: 2011-11-14
• [Presentation] Effects of Selective Mineralocorticoid Receptor Blocker Eplerenone on Endothelial Functionand the Activity of Rho-Associated Kinase in Patients with Essential Hypertension (2011)
  • Author(s): Noritaka Fujimura, Yukihito Higashi, Yumiko Iwamoto, Tatsuya Maruhashi, Shinsuke Mikami, Naomi Idei, Takayuki Hidaka, Kensuke Noma, James K Liao, Yasuki Kihara
  • Organizer: 80^<th> Scientific Sessions, American Heart Association
  • Place of Presentation: Orlando, FA. USA
  • Year and Date: 2011-11-13
• [Presentation] 歯周病と血管内皮機能 (2011)
  • Author(s): 東幸仁
  • Organizer: 第54回日本歯周病学会
  • Place of Presentation: 下関
  • Year and Date: 2011-09-24
• [Presentation] 内皮機能評価:その実際と意義 (2011)
  • Author(s): 東幸仁
  • Organizer: 第59回日本心臓病学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-09-23
• [Presentation] 心臓が動脈・血管に与える影響(FMD):心不全とFMD (2011)
  • Author(s): 東幸仁
  • Organizer: 第84回日本超音波学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-28
• [Presentation] FMD測定とNADPH oxidase欠損症患者からの教訓 (2011)
  • Author(s): 東幸仁
  • Organizer: 第11回日本NO学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-14
• [Presentation] How to MeasureEndothelial Function in Patients with Hypertension : from Plethysmograhy, FMD, and Biomarkers to a New Device (2011)
  • Author(s): Yukihito Higashi
  • Organizer: 第75回日本循環器学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-19
• [Presentation] 血管内皮機能を捉える (2011)
  • Author(s): 東幸仁
  • Organizer: 第11回動脈硬化学会教育フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2011-02-06
• [Presentation] Role of Endothelial Function in Atherosclerosis. The 18th Annual Meeting of the JapaneseVascular Biology and Medicine Organization (2010)
  • Author(s): Yukihito Higashi
  • Organizer: The 8^<th> Korea-JapanJoint Symposium on Vascular Biology
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2010-12-03
• [Presentation] Endothelial Function and Oxidative Stress in X-Linked, gp91phox Deficiency (2010)
  • Author(s): Yukihito Higashi, Junko Soga, Noritaka Fujimura, Masao Kobayash
  • Organizer: Chronic GranulomatousDisease. 79th Scientific Sessions
  • Place of Presentation: Chicago, IL. USA
  • Year and Date: 2010-11-14
• [Presentation] Oxidative Stressand NO in Cardiovascular Disease (2010)
  • Author(s): Yukihito Higashi
  • Organizer: The 10^<th> International Conference on theBiology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-06-17
• [Presentation] Therapeutic Strategy for Peripheral Arterial Disease : Pharmacological Therapy and Angiogenesis. Roles of serotonin andnitric oxide (2009)
  • Author(s): Yukihito Higashi
  • Organizer: 10^<th> International Symposium on Mechanisms on Vasodilation
  • Place of Presentation: Matsushima, Japan
  • Year and Date: 2009-06-01
• [Patent(Industrial Property Rights)] 血管内皮機能評価装置 (2011)
  • Inventor(s): 辻敏夫、吉栖正雄、東幸仁、河本昌志、小沢秀夫、鵜川貞二、高柳恒夫、森本陽香、久保諒祐
  • Industrial Property Rights Holder: 日本光電株式会社、国立大学法人広島大学
  • Industrial Property Number: 特許P10636NK
  • Filing Date: 2011-12-19
• [Patent(Industrial Property Rights)] PGC-1の発現制御装置、並びに虚血性疾患の治療装置及び治療方法 (2009)
  • Inventor(s): 東幸仁、久保裕嗣、隅田潔、西村嘉博、新実信夫
  • Industrial Property Rights Holder: 国立大学法人広島大学、日本シグマックス株式会社
  • Industrial Property Number: PCT/ JP2009/ 006025
  • Filing Date: 2009-11-11
  • Overseas
• [Patent(Industrial Property Rights)] 血管壁モニタリング装置、血管壁モニタリング用プログラム及びコンピュター読み込み可能な記録媒体 (2009)
  • Inventor(s): 辻敏夫、吉栖正雄、河本昌志、東幸仁、佐伯昇、中村隆治、アブドゲニクトュルク、河野曜暢、堀内徹也、鵜川貞二
  • Industrial Property Rights Holder: 日本光電株式会社、国立大学法人広島大学
  • Industrial Property Number: 特許09P10448
  • Filing Date: 2009-11-26