Development of therapies for severe ischemic cardiomyopathy to substute heart transplantation

2013 Fiscal Year Final Research Report

• Project/Area Number: 25670390
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokushima
• Principal Investigator: SATA Masataka 徳島大学, ヘルスバイオサイエンス研究部, 教授 (80345214)
• Project Period (FY): 2013-04-01 – 2014-03-31
• Keywords: 動脈硬化、 / アディポサイトカイン / 脂肪組織 / 分子血管病態学 / バイパス手術

Research Abstract

The only effective therapy for ischemic cardiomyopathy is heart transplantation. However, only limited numbers of donors are available in Japan. Therefore, we tried to establish a new strategy to substitute heart transplantation. Histological analysis of human endarterectomy samples and epicardial fat obtained during cardiac bypass surgery revealed enhanced infiltration of inflammatory cells such as macrophages and T cells not only in vessel wall but also in perivascular adipose tissues. We also found that interaction between cell-free DNA released from adipocytes and TLR9 on macrophages plays a crucial role in chronic inflammation in adipose tissues. Based on these observations, we started to develop a new surgical strategy to treat patients with ischemic cardiomyopathy by reconstructing coronary artery with exogenous artery and subcutaneous adipose tissues.

Research Products

• [Journal Article] Beneficial effect of a synthetic prostacyclin agonist, ONO-1301, in rat autoimmune myocarditis model (2013)
  • Author(s): Hirata Y, Kurobe H, Uematsu E, Yagi S, Soeki T, Yamada H, Fukuda D, Shimabukuro M, Nakayama M, Matsumoto K, Sakai Y, Kitagawa T, Sata M
  • Journal Title: Eur J Pharmacol Volume: 699巻 Pages: 81-87
  • DOI: 10.1016/j.ejphar.2012.11.045
  • Peer Reviewed
• [Journal Article] Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury (2013)
  • Author(s): Hirata Y, Kurobe H, Nishio C, Tanaka K, Fukuda D, Uematsu E, Nishimoto S, Soeki T, Harada N, Sakaue H, Kitagawa T, Shimabukuro M, Nakaya N, Sata M
  • Journal Title: Eur J Pharmacol Volume: 699巻 Pages: 106-111
  • DOI: 10.1016/j.ejphar.2012.11.057
  • Peer Reviewed
• [Journal Article] Growth-associated hyperphosphatemia in young recipients accelerates ao Growth-associated hyperphosphatemia in young recipients accelerates aortic allograft calcification in a rat model (2013)
  • Author(s): Yamauchi H, Motomura N, Chung UI, Sata M, Takai D, Saito A, Ono M, Takamoto S
  • Journal Title: J Thorac Cardiovasc Surg Volume: 145巻 Pages: 522-530
  • DOI: 10.1016/j.jtcvs.2012.03.010
  • Peer Reviewed
• [Journal Article] Eosinophilic myocarditis due to churg-strauss syndrome with markedly elevated eosinophil cationic protein (2013)
  • Author(s): Hara T, Yamaguchi K, Iwase T, Kadota M, Bando M, Ogasawara K, Bando S, Ise T, Niki T, Ueda Y, Tomita N, Taketani Y, Yamada H, Soeki T, Wakatsuki T, Sata M
  • Journal Title: Int Heart J Volume: 54巻 Pages: 51-53
  • DOI: 10.1536/ihj.54.51
  • Peer Reviewed
• [Journal Article] Ulcer-like projection caused by a penetrating branch to the bronchial artery (2013)
  • Author(s): Ise T, Fujioka K, Iwase T, Hotchi J, Akaike M, Sata M
  • Journal Title: J Am Coll Cardiol Volume: 61巻 Pages: e147
  • DOI: 10.1016/j.jacc.2012.10.047
  • Peer Reviewed
• [Journal Article] Constrictive pericarditis with intrapericardial abscess (2013)
  • Author(s): Hara T, Yamada H, Takashima A, Yamasaki H, Ogasawara K, Bando S, Ise T, Niki T, Kusunose K, Ueda Y, Tomita N, Yamaguchi K, Taketani Y, Iwase T, Soeki T, Wakatsuki T, Horiguchi H, Sakashita N, Sata M
  • Journal Title: Circ J Volume: 77巻 Pages: 786-788
  • DOI: 10.1253/circj.CJ-12-1098
  • Peer Reviewed
• [Journal Article] Perivascular adipose tissue-secreted angiopoietin-like protein2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury (2013)
  • Author(s): Tian Z, Miyata K, Tazume H, Sakauguchi H, Kadomatsu T, Horio E, Takahashi O, Komohara Y, Araki K, Hirata Y, Tabata M, Takanashi S, Takeya M, Hao H, Shimabukuro M, Sata M, Kawasuji M, Oike Y
  • Journal Title: J Mol Cell Cardiol Volume: 57巻 Pages: 1-12
  • DOI: 10.1016/j.yjmcc.2013.01.004
  • Peer Reviewed
• [Journal Article] Spectacular migration of a central venous catheter into the pulmonary artery (2013)
  • Author(s): Hara T, Sata M
  • Journal Title: Heart Asia Volume: 5巻 Pages: 42-43
  • DOI: 10.1136/heartasia-2013-010287
  • Peer Reviewed
• [Journal Article] A novel doppler echocardiographic index integrating left and right ventricular function is superior to conventional indices for predicting adverse outcome of acute myocardial infarction (2013)
  • Author(s): Fukuda Y, Soeki T, Sata M
  • Journal Title: J Med Invest Volume: 60巻 Pages: 97-105
  • DOI: 10.2152/jmi.60.97
  • Peer Reviewed
• [Journal Article] Ectopic fat deposition and global cardiometabolic risk : New paradigm in cardiovascular medicine (2013)
  • Author(s): Shimabukuro M, Kozuka C, Taira T, Yabiku K, Dagvasumberel M, Ishida M, Matsumoto S, Yagi Y, Fukuda D, Yamakawa K, Higa M, Soeki T, Yoshida H, Masuzaki H, Sata M
  • Journal Title: J Med Invest Volume: 60巻 Pages: 1-14
  • DOI: 10.2152/jmi.60.1
  • Peer Reviewed
• [Journal Article] Interval from the onset of transmitral flow to annular velocity is a marker of LV filling pressure (2013)
  • Author(s): Kusunose K, Yamada H, Nishio S, Tomita N, Niki T, Yamaguchi K, Taketani Y, Iwase T, Soeki T, Wakatsuki T, Sata M
  • Journal Title: JACC Cardiovasc Imaging Volume: 6巻 Pages: 528-530
  • DOI: 10.1016/j.jcmg.2012.10.025
  • Peer Reviewed
• [Journal Article] Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis (2013)
  • Author(s): Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S, Sata M
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 33巻 Pages: 1077-1084
  • DOI: 10.1161/ATVBAHA.112.300829
  • Peer Reviewed
• [Journal Article] Patent foramen ovale diagnosed by real-time three-dimensional contrast transesophageal echocardiography : A case report (2013)
  • Author(s): Tomita N, Yamada H, Nishio S, Tamai R, Kusunose K, Hayashi S, Hotchi J, Sata M
  • Journal Title: JC Cases Volume: 7巻 Pages: e91-e92
  • DOI: 10.1016/j.jccase.2012.10.011
  • Peer Reviewed
• [Journal Article] Two cases of acute myocardial infarction during combined chemotherapy in young patients with testicular cancer (2013)
  • Author(s): Kawano N, Yamaguchi K, Niki T, Yamamoto T, Iwase T, Taketani T, Ise T, Yamada H, Soeki T, Wakatsuki T, Kawano K, Kakutani K, Sata M
  • Journal Title: JC Cases Volume: 7巻 Pages: e176-e180
  • DOI: 10.1016/j.jccase.2013.02.009
  • Peer Reviewed
• [Journal Article] Defects of vascular nitric oxide bioavailability in subjects with impaired glucose tolerance : A potential link to insulin resistance (2013)
  • Author(s): Shimabukuro M, Higa N, Tagawa T, Yamakawa K, Sata M, Ueda S
  • Journal Title: Int J Cardiol Volume: 167巻 Pages: 298-300
  • DOI: 10.1016/j.ijcard.2012.09.194
  • Peer Reviewed
• [Journal Article] Pharmacology of aldosterone and the effects of mineralocorticoid receptor blockade on cardiovascular systems (2013)
  • Author(s): Yagi S, Akaike M, Aihara KI, Fukuda D, Ishida M, Ise T, Niki T., Sumitomo-Ueda Y, Yamaguchi K, Iwase T, Taketani Y, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Sata M
  • Journal Title: Acta Cardiol Sin Volume: 29巻 Pages: 201-207
  • Peer Reviewed
• [Journal Article] Expanded roles of the renin-angiotensin system (2013)
  • Author(s): Fukuda D, Sata M
  • Journal Title: Hypertens Res Volume: 36巻 Pages: 586-587
  • DOI: 10.1038/hr.2013.27
  • Peer Reviewed
• [Journal Article] Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling (2013)
  • Author(s): Yoshida S, Aihara KI, Ikeda Y, Sumitomo-Ueda Y, Uemoto R, Ishikawa K, Ise T, Yagi S, Iwase T, Mouri Y, Sakari M, Matsumoto T, Takeyama KI, Akaike M, Matsumoto M, Sata M, Walsh K, Kato S, Matsumoto T
  • Journal Title: Circulation Volume: 128巻 Pages: 60-71
  • DOI: 10.1161/CIRCULATIONAHA
  • Peer Reviewed
• [Journal Article] A case of successful use of microsnare to hold and pull the retrograde guidewire for the intervention to peripheral chronic total occlusion (2013)
  • Author(s): Hara T, Wakatsuki T, Taketani Y, Yamaguchi K, Iwase T, Sata M
  • Journal Title: Cardiovasc Interv Ther Volume: 28巻 Pages: 287-290
  • DOI: 10.1007/s12928-013-0158-z
  • Peer Reviewed
• [Journal Article] Role of macrophage-derived hypoxia-inducible factor (HIF)-1α as a mediator of vascular remodeling (2013)
  • Author(s): Nakayama T, Kurobe H, Sugasawa N, Kinoshita H, Higashida M, Matsuoka Y, Yoshida Y, Hirata Y, Sakata M, Maxfield MW, Shimabukuro M, Takahama Y, Sata M, Toshiaki T, Tetsuya K, Tomita S
  • Journal Title: Cardiovasc Res Volume: 99巻 Pages: 705-715
  • DOI: 10.1093/cvr/cvt146
  • Peer Reviewed
• [Journal Article] Unique remodeling processes after vascular injury in intracranial arteries : analysis using a novel mouse model (2013)
  • Author(s): Shimamura M, Nakagami H, Sata M, Takaoka M, Azuma J, Kiomy Osako M, Koriyama H, Kurinami H, Wakayama K, Miyake T, Morishita R
  • Journal Title: J Cereb Blood Flow Metab Volume: 33巻 Pages: 1153-1159
  • DOI: 10.1038/jcbfm.2013.62
  • Peer Reviewed
• [Journal Article] Miglitol, α-glycosidase inhibitor, reduces visceral fat accumulation and cardiovascular risk factors in subjects with the metabolic syndrome : A randomized comparable study (2013)
  • Author(s): Shimabukuro M, Higa M, Yamakawa K, Masuzaki H, Sata M
  • Journal Title: Int J Cardiol Volume: 167巻 Pages: 2108-2118
  • DOI: 10.1016/j.ijcard.2012.05.109
  • Peer Reviewed
• [Journal Article] Blockade of CTP synthase regulates SMC and EC proliferation differentially (2013)
  • Author(s): Tanaka K, Sata M
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 33巻 Pages: 2286-2287
  • DOI: 10.1161/ATVBAHA.113.302315
  • Peer Reviewed
• [Journal Article] HMGB1 plays a critical role in vascular inflammation and lesion formation via toll-like receptor 9 (2013)
  • Author(s): Hirata Y, Kurobe H, Higashida M, Fukuda D, Shimabukuro M, Higashikuni Y, Kitagawa T, Sata M
  • Journal Title: Atherosclerosis Volume: 231巻 Pages: 227-233
  • DOI: 10.1016/j.atherosclerosis.2013.09.010
  • Peer Reviewed
• [Journal Article] Protective effects of selective mineralocorticoid receptor antagonist against aortic aneurysm progression in a novel murine model (2013)
  • Author(s): Kurobe H, Hirata Y, Matsuoka Y, Sugasawa N, Higashida M, Nakayama T, Maxfield MW, Shimabukuro M, Kitagawa T, Sata M
  • Journal Title: J Surg Res Volume: 185巻 Pages: 455-462
  • DOI: 10.1016/j.jss.2013.05.002
  • Peer Reviewed
• [Journal Article] Quercetin glucosides promote ischemia-induced angiogenesis, but do not promote tumor growth (2013)
  • Author(s): Sumi M, Tateishi N, Shibata H, Ohki T, Sata M
  • Journal Title: Life Sciences Volume: 93巻 Pages: 814-819
  • DOI: 10.1016/j.lfs.2013.09.005
  • Peer Reviewed
• [Journal Article] Renin-angiotensin-aldosterone system has a pivotal role in cognitive impairment (2013)
  • Author(s): Yagi S, Akaike M, Ise T, Ueda Y, Iwase T, Sata M
  • Journal Title: Hypertens Res Volume: 36巻 Pages: 753-758
  • DOI: 10.1038/hr.2013.51
  • Peer Reviewed
• [Journal Article] Azelnidipine suppresses the progression of aortic aneurysm in wild mice model through anti-inflammatory effects (2013)
  • Author(s): Kurobe H, Matsuoka Y, Hirata Y, Sugasawa N, Maxfield MW, Sata M, Kitagawa T
  • Journal Title: J Thorac Cardiovasc Surg Volume: 146巻 Pages: 1501-1508
  • DOI: 10.1016/j.jtcvs.2013.02.073
  • Peer Reviewed
• [Journal Article] Toll-like receptor-2 mediates adaptive cardiac hypertrophy in response to pressure overload through interleukin-1β upregulation via nuclear factor κB activation (2013)
  • Author(s): Higashikuni Y, Tanaka K, Kato M, Nureki O, Hirata Y, Nagai R, Komuro I, Sata M
  • Journal Title: J Am Heart Assoc Volume: 2巻 Pages: e000267
  • DOI: 10.1161/JAHA.113.000267
  • Peer Reviewed
• [Journal Article] Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein (2013)
  • Author(s): Soeki T, Niki T, Uematsu E, Bando S, Matsuura T, Kusunose K, Ise T, Ueda Y, Tomita N, Yamaguchi K, Koshiba K, Yagi S, Fukuda D, Taketani Y, Iwase T, Yamada H, Wakatsuki T, Akaike M, Shimabukuro M, Kishimoto I, Kangawa K, Sata M
  • Journal Title: Heart Vessels Volume: 28巻 Pages: 795-801
  • DOI: 10.1007/s00380-013-0333-2
  • Peer Reviewed
• [Journal Article] Effects of telmisartan on inflammatory cytokines and the coronary plaque component as assessed on integrated backscatter intravascular ultrasound in hypertensive patients (2013)
  • Author(s): Yamaguchi K, Wakatsuki T, Soeki T, Niki T, Taketani Y, Oeduka H, Kusunose K, Ise T, Iwase T, Yamada H, Sata M
  • Journal Title: Circ J Volume: 78巻 Pages: 240-247
  • DOI: 10.1253/circj.CJ-13-0741
  • Peer Reviewed
• [Presentation] Macrophage Toll-like Receptor 9 Signaling Contributes to the Development of Insulin Resistance through the Promotion of Inflammation in Adipose Tissue (2013)
  • Author(s): Nishimoto S, Fukuda D, Shimabukuro M, Yagi S, Soeki T, Sakaue H, Nakaya Y, Sata M
  • Organizer: AHA Scientific Sessions 2013
  • Place of Presentation: ダラスコンベンションセンター(Dallas, America)
  • Year and Date: 20131116-20
• [Presentation] Decreased Local Hypercoagulation after Implantation of Everolimus-Eluting and Zotarolimus-Eluting Stents Compared with Early-Generation Drug-Eluting Stents in patients with stable angina (2013)
  • Author(s): Yamaguchi K, Wakatsuki T, Ise T, Tobiume T, Yagi S, Iwase T, Yamada H, Soeki T, Sata M
  • Organizer: AHA Scientific Sessions 2013
  • Place of Presentation: ダラスコンベンションセンター(Dallas, America)
  • Year and Date: 20131116-20
• [Presentation] Rivaroxaban, A Novel Oral Anticoagulant, Attenuates Plaque Progression in ApoE-Deficient Mice Through the Inhibition of Pro-Inflammatory Activation of Macrophages (2013)
  • Author(s): Hara T, Fukuda D, Tanaka K, Higashikuni Y, Hirata Y, Ise T, Tobiume T, Yamaguchi K, Yagi S, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Sata M
  • Organizer: AHA Scientific Sessions 2013
  • Place of Presentation: ダラスコンベンションセンター(Dallas, America)
  • Year and Date: 20131116-20
• [Book] (4. 治療薬総論 硝酸薬)今日の循環器疾患治療指針 第3版(編集 井上博、許俊鋭、檜垣實男、代田浩之、筒井裕之) (2013)
  • Author(s): 篠山重威、井上博、能澤孝、清水昭彦、宇野漢成、竹中克、柴崎誠一、苅尾七臣、星出聡、山下武志、山科章、越川めぐみ、池田宇一、今村浩、椎名一紀、堀進悟、坂本哲也、野々木宏、竹谷善雄、佐田政隆, 他
  • Total Pages: 938(162-165)
  • Publisher: 医学書院
• [Book] (血管機能を改善する効果があります)そうだったんだ!脂肪酸(編集 伊藤浩) (2013)
  • Author(s): 伊藤浩、板倉弘重、岩崎仁、島野仁、才田恵美、近藤和雄、山岸良匡、磯博康、佐久間一郎、松島照彦、野村昌作、村崎かがり、吉田博、石川雄一、原知也、佐田政隆、栗原毅、冨山博史、沖美環、平野賢一, 他
  • Total Pages: 186(67-70, 76)
  • Publisher: 文光堂
• [Remarks] 徳島大学大学院ヘルスバイオサイエンス研究部循環器内科学
  • URL: http://square.umin.ac.jp/TOKUSHIM/