NOTCH-FABP PATHWAY REGULATES TRANS-ENDOTHELIAL FATTY ACID TRANSPORT IN HEART

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590877
• 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: Gunma University
• Principal Investigator: ISO Tatsuya Gunma University, 大学院・医学系研究科, 助教 (10400756)
• Co-Investigator(Kenkyū-buntansha): KURABAYASHI Masahiko 群馬大学, 大学院・医学系研究科, 教授 (00215047)
• Project Period (FY): 2008 – 2010
• Keywords: 毛細血管 / 内皮細胞 / 脂肪酸代謝 / Notchシグナル / FABP4 / FABP5 / PPAR-・

Research Abstract

Thus far, energy metabolism has been mostly studied with energy-consuming parenchymal cells. In our project, we focused on muscle-type continuous capillary. FABP4/FABP5 expressed in endothelial cells of the muscle-type continuous capillary plays a pivotal role in trans-endothelial FA transport. Components of Notch signaling and PPAR-・ expressed in capillary endothelial cells regulate trans-endothelial fatty acid transport via induction of FABP4. Our study proposes the concept of trans-endothelial fatty acid transport, which may provide a new approach to treat metabolic diseases.

Research Products

• [Journal Article] Multiple Spontaneous Coronary Artery Ruptures and Cardiac Tamponade in Vascular Ehlers-Danlos Syndrome. (2010)
  • Author(s): Yoshiaki Ohyama, Tatsuya Iso,, Adriana Carolina Vargas Nino, Masaru Obokata, Rieko Takahashi, Wataru Okumura, Akihiko Nakano, Masao Amano, Isao Naito, Masamitsu Takatama, Masahiko Kurabayashi
  • Journal Title: Journal of Cardiology Cases (in press)
  • Peer Reviewed
• [Journal Article] Post myocardial ischemia-associated torsades de pointes in a patient carrying a KCNQ1 G643S variant. (2010)
  • Author(s): Nakajima T, Kaneko Y, Saito A, Irie T, Kato T, Iso T, Kurabayashi M
  • Journal Title: Intern Med. 49(23)(Epub 2010 Dec 1.) Pages: 2587-91
  • Peer Reviewed
• [Journal Article] Notch Induces Myofibroblast Differentiation of Alveolar Epithelial Cells via TGF-ss/Smad3 Pathway. (2010)
  • Author(s): Aoyagi-Ikeda K, Maeno T, Matsui H, Ueno M, Hara K, Aoki Y, Aoki F, Shimizu T, Doi H, Kawai-Kowase K, Iso T,, Suga T, Arai M, Kurabayashi M
  • Journal Title: Am J Respir Cell Mol Biol. (Epub ahead)
  • Peer Reviewed
• [Journal Article] Aborted cardiac arrest in a patient carrying KCNE1 D85N variant during the postpartum period. (2010)
  • Author(s): Nakajima T, Kaneko Y, Manita M, Iso T, Kurabayashi M
  • Journal Title: Intern Med. 49(17) Pages: 1875-8
  • Peer Reviewed
• [Journal Article] Fibroblast Growth Factor 2 Induces Osteogenic Differentiation through a Runx2 Activation in Vascular Smooth Muscle Cells. (2010)
  • Author(s): Nakahara T, Sato H, Shimizu T, Tanaka T, Matsui H, Kawai-Kowase K, Sato M, Iso T, Arai M, Kurabayashi M
  • Journal Title: Biochem Biophys Res Commun. 394(2) Pages: 243-8
  • Peer Reviewed
• [Journal Article] Marked high density lipoprotein deficiency due to apolipoprotein A-I Tomioka (codon 138 deletion). (2009)
  • Author(s): Wada M, Iso T,, Asztalos BF, Takama N, Nakajima T, Seta Y, Kaneko K, Taniguchi Y, Kobayashi H, Nakajima K, Schaefer EJ, Kurabayashi M
  • Journal Title: Atherosclerosis. 207(1) Pages: 157-161
  • Peer Reviewed
• [Journal Article] Notch signaling induces osteogenic differentiation and mineralization of vascular smooth muscle cells : role of Msx2 gene induction via Notch-RBP-Jk signaling. (2009)
  • Author(s): Shimizu T, Tanaka T, Iso T, Doi H, Sato H, Kawai-Kowase K, Arai M, Kurabayashi M
  • Journal Title: Arterioscler Thromb Vasc Biol. 29(7) Pages: 1104-11
  • Peer Reviewed
• [Journal Article] Notch signaling regulates the differentiation of bone marrow-derived cells into smooth muscle-like cells during arterial lesion formation. (2009)
  • Author(s): Doi H, Iso T, Shiba Y, Sato H, Yamazaki M, Oyama Y, Akiyama H, Tanaka T, Tomita T, Arai M, Takahashi M, Ikeda U, Kurabayashi M
  • Journal Title: Biochem Biophys Res Commun. 381 Pages: 654-659
  • Peer Reviewed
• [Journal Article] IAS1 Mediates TGF{beta}-Induced SM {alpha}-Actin Gene Expression Through Inhibition of KLF4 Function-Expression by Protein Sumoylation. (2009)
  • Author(s): Kawai-Kowase K, Ohshima T, Matsui H, Tanaka T, Shimizu T, Iso T, Arai M, Owens GK, Kurabayashi M
  • Journal Title: Arterioscler Thromb Vasc Biol. 29(1) Pages: 99-106
  • Peer Reviewed
• [Journal Article] Prostaglandin F2alpha inhibits SERCA2 gene transcription through an induction of Egr-1 in cultured neonatal rat cardiac myocytes. (2008)
  • Author(s): Hara S, Arai M, Tomaru K, Doi H, Koitabashi N, Iso T, Watanabe A, Tanaka T, Maeno T, Suga T, Yokoyama T, Kurabayashi M
  • Journal Title: Int Heart J. 49(3) Pages: 329-42
  • Peer Reviewed
• [Journal Article] Effects of a stable prostacyclin analogue beraprost sodium on VEGF and PAI-1 gene expression in vascular smooth muscle cells. (2008)
  • Author(s): Atsuta H, Uchiyama T, Kanai H, Iso T, Tanaka T, Suga T, Maeno T, Arai M, Nagai R, Kurabayashi M
  • Journal Title: Int J Cardiol. 132(3) Pages: 411-8
  • Peer Reviewed
• [Journal Article] Runx2 Represses Myocardin-mediated Differentiation and Facilitates Osteogenic Conversion of Vascular Smooth Muscle Cells. (2008)
  • Author(s): Tanaka T, Sato H, Doi H, Yoshida CA, Schimizu T, Matsui H, Yamazaki M, Akiyama H, Kawai-Kowase K, Iso T, Komori T, Arai M, Kurabayashi M
  • Journal Title: Mol Cell Biol. 28(3) Pages: 1147-60
• [Journal Article] PPARsと動脈硬化 (2008)
  • Author(s): 磯達也、倉林正彦
  • Journal Title: 炎症と免疫 16 Pages: 67-73
• [Journal Article] 胸痛 (2008)
  • Author(s): 磯達也
  • Journal Title: 看護に役立つ疾患・症候辞典 Pages: 1501-1505
• [Presentation] Peroxisome Proliferator Activated Receptor Gamma Regulates Trans-endothelial Fatty Acid Transport via Induction of Fatty Acid Binding Protein 4 and Fatty Acid Translocase in Capillary Endothelial Cells in Heart and Adiose Tissue. (2010)
  • Author(s): Goto K, Tatsuya Iso T, Hanaoka H, Suga T, Matsui H, Arai M, Endo K, Frank J Gonzalez, Kurabayashi M.
  • Organizer: Annual meeting of American Heart Association, Chicago
  • Place of Presentation: McCormick Place (Chicago, USA).
  • Year and Date: 2010-11-17
• [Presentation] Notch signaling enhances BMP2-induced osteogenic differentiation of vascular smooth muscle cells and vascular calcification (2010)
  • Author(s): Shimizu T, Tanaka T, Iso T, Kurabayashi M.
  • Organizer: XX^<th> World Congress International Society for Heart Research (ISHR)
  • Place of Presentation: Kyoto International Conference Center.(Kyoto)
  • Year and Date: 2010-05-16
• [Presentation] Elevated stearoyl-CoA desaturase-1 expression in obese and diabetic heart plays a protective role against fatty acid-induced cardiac dysfunction (2010)
  • Author(s): Matsui H, Yokoyama T, Iijima D, Maniwa M, Iso T, Arai M, Kurabayashi M.
  • Organizer: XX^<th> World Congress International Society for Heart Research (ISHR)
  • Place of Presentation: Kyoto International Conference Center (Kyoto).
  • Year and Date: 2010-05-16
• [Presentation] Notch-peroxisome proliferator activated receptor-gamma2 pathway regulates transendothelial fatty acid transport in capillary endothelial cells in heart (2010)
  • Author(s): Goto K, Iso T, Suga T, Matsui H, Arai M, Kurabayashi M.
  • Organizer: XX^<th> World Congress International Society for Heart Research (ISHR)
  • Place of Presentation: Kyoto International Conference Center.(Kyoto)
  • Year and Date: 2010-05-16
• [Presentation] A possible role of transendothelial glycerol transport through aquaporin 7 regulated by peroxisome proliferated activator reveptor-gamma (2010)
  • Author(s): Haque A, Iso T, Kunimoto F, Saito S, Kurabayashi M.
  • Organizer: XX^<th> World Congress International Society for Heart Research (ISHR)
  • Place of Presentation: Kyoto International Conference Center.(Kyoto)
  • Year and Date: 2010-05-16
• [Presentation] Muscle-type capillary endothelial cells actively transport fatty acids via intracellular fatty acid binding protein-4 and -5 (2010)
  • Author(s): Iso T, Maeda K, Hanaoka H, Suga T, Matsui H, Goto K, Arai M, Endo K, Gokhan H, Kurabayashi M.
  • Organizer: XX^<th> World Congress International Society for Heart Research (ISHR)
  • Place of Presentation: Kyoto International Conference Center.(Kyoto)
  • Year and Date: 2010-05-14
• [Presentation] Runx2 suppresses atrial and B-type natriuretic peptide gene expression in rat cardiac myocytes. (2010)
  • Author(s): Nakahara T, Shimizu T, Tanaka T, Kowase K, Iso T, Arai M, Kurabayashi M.
  • Organizer: XX^<th> World Congress International Society for Heart Research (ISHR)
  • Place of Presentation: Kyoto International Conference Center.(Kyoto)
  • Year and Date: 2010-05-13
• [Presentation] Steroyl-CoA desaturase-1 has a protective effect against saturated fatty acids-induced osteogenic differentiation and apoptosis in vascular smooth muscle cells (2010)
  • Author(s): Matsui H, Yokoyama T, Gotoh Y, Iso T, Arai M, Kurabayashi M.
  • Organizer: XX^<th> World Congress International Society for Heart Research (ISHR)
  • Place of Presentation: Kyoto International Conference Center(Kyoto).
  • Year and Date: 2010-05-13
• [Presentation] Osteogenic Transcription Factor Runx2 Suppresses Atrial and B-type Natriuretic Peptide Gene Expression in Rat Cardiac Myocytes. (2010)
  • Author(s): Takehiro Nakahara, Takehisa Shimizu, Toru Tanaka, Keiko Kowase, Tatsuya Iso, Masashi Arai, Masahiko Kurabayashi
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kyoto International Conference Center (Kyoto).
  • Year and Date: 2010-03-07
• [Presentation] Identification of Four Novel Mutations in SCN5A in Brugada Syndrome. (2010)
  • Author(s): Tadashi Nakajima, Yoshiaki Kaneko, Akohiko Saitoh, Tadanobu Irie, Tatsuya Iso, Masahiko Kurabayashi
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kyoto International Conference Center(Kyoto).
  • Year and Date: 2010-03-07
• [Presentation] Peroxisome Proliferator Activated Receptor-Alpha Regulates Transendothelial Fatty Acid Transport in Capillary Endothelial Cells in Heart. (2010)
  • Author(s): Yuji Shinagawa, Tatsuya Iso, Hiroki Matsui, Tomoyuki Yokoyama, Masahiko Kurabayashi
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kyoto International Conference Center(Kyoto).
  • Year and Date: 2010-03-07
• [Presentation] Bone Morphogenetic Proteins Works as Instructive Signals to Specify Smooth Muscle Cell Differentiation Induced by Notch Signaling. (2010)
  • Author(s): Takehisa Shimizu, Toru Tanaka, Takehiro Nakahara, Tatsuya Iso, Masashi Arai, Masahiko Kurabayashi
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: KyotoInternational Conference Center(Kyoto).
  • Year and Date: 2010-03-06
• [Presentation] Muscle-Type Capillary Endothelial Cells Actively Transport Fatty Acids via Intracellular Fatty Acid Binding Protein-4 and -5. (2010)
  • Author(s): Tatsuya Iso, Kazuhisa Maeda, Hirofumi Hanaoka, Toshihiro Suga, Hiroki Matsui, Kosaku Goto, Masashi Arai, Keigo Endo, Gohkan Hotamisligil, Masahiko Kurabayashi
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kyoto International Conference Center(Kyoto).
  • Year and Date: 2010-03-06
• [Presentation] Notch and BMP2 Signalings Cooperatively Enhance Runx2-mediated Induction of Osteoblastic Phenotype in Vascular Smooth Muscle Cells. (2010)
  • Author(s): Takehisa Shimizu, Toru Tanaka, Keiko Kowase, Tatsuya Iso, Masashi Arai, Masahiko Kurabayashi
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kyoto International Conference Center(Kyoto).
  • Year and Date: 2010-03-05
• [Presentation] Runx2 Inhibits TGF・-induced Connective Tissue Growth Factor Gene Expression Through Physical Association with Smad3 in Vascular Smooth Muscle Cells (2009)
  • Author(s): Yoshiaki Oyama, Toru Tanaka, Takehisa Shimizu, Hiroko Sato, Norimichi Koitabashi, Hiroshi Doi, Tatsuya Iso, Masashi Arai, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Orange County Convention Center(Orlando, USA).
  • Year and Date: 2009-11-18
• [Presentation] Notch-Peroxisome Proliferator Activated Receptor Gamma2 Pathway Regulates Transendothelial Fatty Acid Transport via Induction of Fatty Acid Binding Protein 4 and Fatty Acid Translocase in Capillary Endothelial Cells in Heart. (2009)
  • Author(s): Kosaku Goto, Tatsuya Iso, Toshihiro Suga, Hiroki Matsui, Masashi Arai, Frank J Gonzalez, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Orange County Convention Center(Orlando, USA).
  • Year and Date: 2009-11-17
• [Presentation] Bone Morphogenetic Protein-2 (BMP-2) and BMP-7 Act as Instructive Factors to Specify Notch Signaling Controlling Smooth Muscle Cell Phenotype. (2009)
  • Author(s): Takehisa Shimizu, Toru Tanaka, Tatsuya Iso, Keiko Kawai-Kowase, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Orange County Convention Center(Orlando, USA).
  • Year and Date: 2009-11-17
• [Presentation] Muscle-Type Capillary Endothelial Cells Actively Transport Fatty Acids via Intracellular Fatty Acid Binding Protein-4 and-5. (2009)
  • Author(s): Tatsuya Iso, Kazuhisa Maeda, Hirofumi Hanaoka, Toshihiro Suga, Hiroki Matsui, Kosaku Goto, Masashi Arai, Keigo Endo, Gohkan Hotamisligil, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Orange County Convention Center(Orlando, USA).
  • Year and Date: 2009-11-16
• [Presentation] Increased Stearoyl-CoA Desaturase-1 Expression in Obese and Diabetic Heart Plays a Protective Role Against Fatty Acid-Induced Cardiac Dysfunction (2009)
  • Author(s): Hiroki Matsui, Tomoyuki Yokoyama, Daisuke Iijima, Kenichi Sekiguchi, Tatsuya Iso, Masahi Arai, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Orange County Convention Center(Orlando, USA).
  • Year and Date: 2009-11-16
• [Presentation] Osteogenic Transcription Factor Runx2 Suppresses Atrial and B-Type Natriuretic Peptide Gene Expression in Rat Cardiomyocytes : Possible Role of Runx2 in Cardiac Fibrosis. (2008)
  • Author(s): Takahiro Nakahara, Takehisa Shimizu, Keiko Kawai-Kowase, Toru Tanaka, Tatsuya Iso, Masashi Arai, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Ernest N. Morial Convention Center.(New Orleans, USA)
  • Year and Date: 2008-11-11
• [Presentation] Activation of Receptor for advanced-glycation end products (RAGE) induces Notch-Msx2-dependent osteoblastic differentiation of vascular smooth muscle cells. (2008)
  • Author(s): Toshihiro Suga, Tatsuya Iso, Takehisa Shimizu, Toru Tanaka, Sho-ichi Yamagishi, Masashi Arai, Tsutomu Imaizumi, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Ernest N.Morial Convention Center.(New Orleans, USA)
  • Year and Date: 2008-11-11
• [Presentation] Notch signaling Enhances BMP2-induced Msx2 Gene Expression and Vascular Calcification. (2008)
  • Author(s): Takehisa Shimizu, Toru Tanaka, Tatsuya Iso, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Ernest N.Morial Convention Center.(New Orleans, USA)
  • Year and Date: 2008-11-10
• [Presentation] Stearoyl-CoA Desaturase-1 Protects Against Saturated Fatty Acids-Induced Osteogenic Differentiation and Apoptosis of Vascular Smooth Muscle Cells. (2008)
  • Author(s): Hiroki Matsui, Tomoyuki Yokoyama, Kenichi Sekiguchi, Yousuke Gotoh, Tatsuya Iso, Masahi Arai, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Ernest N. Morial Convention Center.(New Orleans, USA)
  • Year and Date: 2008-11-10
• [Presentation] Notch Signaling induces Expression of Fatty Acid Binding Protein 4 via Induction of PPAR-g2 in Capillary Endothelial Cells in Heart. (2008)
  • Author(s): Tatsuya Iso, Toshihiro Suga, Hiroki Matsui, Masashi Arai, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Ernest N.Morial Convention Center.(New Orleans, USA)
  • Year and Date: 2008-11-10
• [Presentation] Notch signaling Directly Targets Msx2 : Possible Role of Notch Signaling in Osteogenic Conversion of Vascular Smooth Muscle Cells and Vascular Calcification (2008)
  • Author(s): Takehisa Shimizu, Toru Tanaka, Tatsuya Iso, Masahiko Kurabayashi
  • Organizer: Annual meeting of American Heart Association
  • Place of Presentation: Ernest N.Morial Convention Center.(New Orleans, USA)
  • Year and Date: 2008-11-09
• [Presentation] Notch signaling contributes to pathogenesis of vascular diseases. (2008)
  • Author(s): Tatsuya Iso
  • Organizer: International Vascular Biology Meeting, Sydney
  • Place of Presentation: Sydney Convention Center(Sydney, Australia).(Invited)
  • Year and Date: 2008-06-04