Mechanisms of hypoxia-induced transformation in endothelial cells

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590335
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: TOMITA Shuhei 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (00263898)
• Co-Investigator(Kenkyū-buntansha): TAMAKI Toshiaki 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (80179879)
• Research Collaborator: NAKAYAMA Taisuke 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 大学院生 ; IMANISHI Masaki 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 大学院生
• Project Period (FY): 2009 – 2011
• Keywords: 分子病態学 / 低酸素

Research Abstract

MCT-induced pulmonary arteries demonstrated binding of pimonidazole, a hypoxia detection agent that binds to regions of hypoxia in the region around vascular walls including lung epithelial cells. Indices of the PAH were significantly alleviated in the Hif-1β+/-mice compared to the control as the following data showed ; the weight ratio of right ventricular to left ventricular with septum was significantly decreased ; the number of pulmonary arteries was significantly increased ; indices of the medial thickness was significantly decreased. The number of musculized pulmonary arteries in MCT-treated Hif-1β+/-mice was significantly decreased compared to that of the control mice. In addition, interestingly, the PAH in wild type mice was ameliorated by administration of bosentan, an endothelin receptor blocker, to the same level of that in Hif-1β+/-mice. These results indicate that the development of MCT-induced PAH was mediated by HIF-1βin endothelial cells.

Research Products

• [Journal Article] Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice (2011)
  • Author(s): Tajima S, Ikeda Y, Sawada K, Yamano N, Horinouchi Y, Kihira Y, Ishizawa K, Izawa-Ishizawa Y, Kawazoe K, Tomita S, Minakuchi K, Tsuchiya K, and Tamaki T
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 302 Pages: E77-E86
  • DOI: doi:10.1152/ajpendo.00033.2011
• [Journal Article] Basic fibroblast growth factor regulates glucose metabolism through glucose transporter 1 induced by hypoxia-inducible factor-1αin adipocytes (2011)
  • Author(s): Kihira Y, Yamano N, Izawa-Ishizawa Y, Ishizawa K, Ikeda Y, Tsuchiya K, Tamaki T, Tomita S
  • Journal Title: Int J Biochem Cell Biol Volume: 43 Pages: 1602-1611
  • DOI: 10.1016/j.biocel.2011.07.009
• [Journal Article] Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular endothelial cells (2011)
  • Author(s): Fukuhara Y, Tsuchiya K, Horinouchi Y, Tajima S, Kihira Y, Hamano S, Kawazoe K, Ikeda Y, Ishizawa K, Tomita S and Tamaki T
  • Journal Title: The Journal of Medical Investigation Volume: 59 Pages: 118-126
  • DOI: doi:10.2152/jmi.58.118
• [Journal Article] Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function (2011)
  • Author(s): Ikeda Y, Tajima S, Yoshida S, Yamano N, Kihira Y, Ishizawa K, Aihara K, Tomita S, Tsuchiya K and Tamaki T
  • Journal Title: Atherosclerosis Volume: 215 Pages: 339-347
  • DOI: doi:10.1016/j.atherosclerosis.2011.01.009
• [Journal Article] Antioxidant effects of photodegradation product of nifedipine (2011)
  • Author(s): Horinouchi Y, Tsuchiya K, Taoka C, Tajima S, Kihira Y, Matsuda Y, Shishido K, Yoshida M, Hamano S, Kawazoe K, Ikeda Y, Ishizawa K, Tomita S, Tamaki T
  • Journal Title: Chem Pharm Bull Volume: 59 Pages: 208-214
  • DOI: doi:10.1248/cpb.59.208
• [Journal Article] Effect of angiotensin II on iron-transporting protein expression and subsequent intracellular labile iron concentration in human glomerular endothelial cells (2010)
  • Author(s): Tajima S, Tsuchiya K, Horinouchi Y, Ishizawa K, Ikeda Y, Kihira Y, Shono M, Kawazoe K, Tomita S, Tamaki T
  • Journal Title: Hypertens Res Volume: 33 Pages: 713-721
  • DOI: doi:10.1038/hr.2010.63
• [Journal Article] Role of Hif-1a in T cells as a negative regulator in development of vascular remodeling (2010)
  • Author(s): Kurobe H, Urata M, Ueno M, Ueki M, Ono S, Izawa-Ishizawa Y, Fukuhara Y, Lei Y, Ripen AM, Kanbara T, Aihara K, Ishizawa K, Akaike M, Gonzalez FJ, Tamaki T, Takahama Y, Yoshizumi M, Kitagawa T, Tomita S
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 30 Pages: 210-217
  • DOI: doi:10.1161/ATVBAHA.109.192666
• [Journal Article] Angiotensin II receptor blocker attenuates PDGF-induced mesangial cell migration in a receptor-independent manne (2010)
  • Author(s): Ishizawa K, Izawa-Ishizawa Y, Dorjsuren N, Miki E, Kihira Y, Ikeda Y, Hamano S, Kawazoe K, Minakuchi K, Tomita S, Tsuchiya K and Tamaki T
  • Journal Title: Nephrol Dial Transpl Volume: 25 Pages: 364-372
  • DOI: doi:10.1093/ndt/gfp520
• [Presentation] Preconditionining of mice with prolyl hydroxylase inhibitor, dimethyloxalylglycine, prevents skin flap necrosis (2011)
  • Author(s): Takaku M, Tomita S, Kihira Y, Hashimoto I, Nakanishi H, Tamaki T.
  • Organizer: AHA scientific sessions 2011
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2011-11-16
• [Presentation] Estrogen action on iron metabolism (2011)
  • Author(s): Ikeda Y, Tajima S, Yamano N, Kihira Y, Ishizawa K, Tomita S, Tsuchiya K, Tamaki T.
  • Organizer: The Endocrine Society 2011
  • Place of Presentation: Boston, USA
  • Year and Date: 2011-11-04
• [Presentation] Glucose Metabolism of Adipocytes is Regulated by Basic Fibroblast Growth Factor via Hypoxia-inducible Factor-1α (2011)
  • Author(s): Yamaguchi K, Kihira Y, Yamano N, Izawa-Ishizawa Y, Ishizawa K, Ikeda Y, Tsuchiya K, Tomita S, Tamaki T
  • Organizer: High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2011-09-28
• [Presentation] Inhibition of Adipocyte Hypertrophy by Deferoxiamine Diabetic KKAy mice (2011)
  • Author(s): Tajima S, Ikeda Y, Yamano N, Tsuchiya K, Ishizawa Y, Kihira Y, Ishizawa K, Kawazoe K, Tomita S, Minakuchi K, Tamaki T.
  • Organizer: High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions
  • Place of Presentation: Florida, USA
  • Year and Date: 2011-09-28
• [Presentation] Smooth Muscle Cell-Specific Hypoxia-Inducible Factor-1αDeficiency Attenuates Angiotensin II-Induced Vascular Remodeling in Mice (2011)
  • Author(s): Imanishi M, Ishizawa K, Kihira Y, Ikeda Y, Yamano Y, Ishizawa Y, Tsuchiya K, Tamaki T, Tomita S
  • Organizer: AHA scientific sessions 2011
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2011-09-28
• [Presentation] Heparin Cofactor II Promotes Angiogenesis via an AMPK-eNOS Signaling Pathway (2011)
  • Author(s): Ikeda Y, Aihara KI, Yoshida S, Kihira Y, Ishizawa K, Izawa-Ishizawa Y, Tomita S, Sata M, Akaike M, Kato S, Matsumoto T, Tamaki T.
  • Organizer: High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions
  • Place of Presentation: Orlando, Florida
  • Year and Date: 2011-09-28
• [Presentation] Hypoxia-inducible Factor-1αDeficiency in Smooth Muscle Cells Suppresses AngiotensinII-induced Vascular Remodeling in Mice (2011)
  • Author(s): Imanishi M, Ishizawa K, Kihira Y, Ikeda Y, Yamano N, Ishizawa Y, Tsuciya K, Tamaki T, Tomita S.
  • Organizer: High Blood Pressure Research Scientific Sessions 2011 Scientific Sessions
  • Place of Presentation: Orlando, Florida
  • Year and Date: 2011-09-28
• [Presentation] Nitorosonifedipine is a new class drug to improves angiotensin II-induced vascular remodeling (2011)
  • Author(s): Ishizawa K, Sakurada T, Imanishi M, Fujii S, Ishizawa Y, Kihira Y, Ikeda Y, Tomita S, Tsuchiya K, Tamaki T
  • Organizer: European Society of Cardiology Congress 2011
  • Place of Presentation: Paris, France
  • Year and Date: 2011-08-27
• [Presentation] Preconditioning of mice with a PHD inhibitor, dimethyloaxylglycine, prevent skin flap necrosis (2011)
  • Author(s): Takaku M, Tomita S, Kurobe H, Hashimoto I, Nakanishi H, Tamaki T
  • Organizer: ISSOT(International Society on Oxygen Transport to Tissue) 2011
  • Place of Presentation: Washington DC
  • Year and Date: 2011-08-25
• [Presentation] Increment intracellular labile iron enhances angiotensin-induced intracellular adhesion molecule-1(ICAM-1) expression in human glomerular endothelial cells (2011)
  • Author(s): Imanishi M, Tajima S, Kihira Y, Ishizawa K, Ikeda Y, Kondo S, Kagami S, Tomita S, Ikeda Y, Tsuchiya K, Tamaki S.
  • Organizer: World Congress of Nephrology 2011
  • Place of Presentation: Vancouver
  • Year and Date: 2011-04-10
• [Presentation] Nitroso-Nifedipine is A New Class Drug to Protect Endotherial Function for Overcoming Organ Damage (2010)
  • Author(s): Ishizawa K, Imanishi M, Horinouchi Y, Fukuhara Y, Izawa-Ishizawa Y, Ikeda Y, Kihira Y, Tomita S, Tsuchiya K, Tamaki T
  • Organizer: The 23rd Scientific Meeting of the International Society of Hypertension GLOBAL CARDIOVASCULAR RISK REDUCTION
  • Place of Presentation: Vancouver
  • Year and Date: 2010-11-23
• [Presentation] IRON DERIVATION AMELIORATES GLUCOSE TOLERANCE THROUGH REDUCTION OF OXIDATIVE STRESS AND INFLAMMATION IN DIABETIC KKAY MICE (2010)
  • Author(s): Tajima S, Ikeda Y, Yamano N, Tsuchiya K, Kihira Y, Ishizawa K, Kawazoe K, Tomita S, Minakuchi K, Tamaki T
  • Organizer: 2010 American Physiological Society Conference Inflammation, Immunity and Cardiovascular Disease
  • Place of Presentation: Colorado
  • Year and Date: 2010-11-07
• [Presentation] Endothelial-targeted hypoxia-inducible factor-1b(HIF-1b) loss-of function alleviates the monocrotaline-induced pulmonary hypertension in mice (2010)
  • Author(s): Tomita S, Urata M, Fukuhara Y, Kihira Y, Ikeda Y, Ishizawa K, Tsuchiya K, Kitagawa T, Tamaki T
  • Organizer: American Heart Association Scientific Sessions 2010
  • Place of Presentation: Chicago, Illinois
  • Year and Date: 2010-11-04
• [Presentation] Iron elimination ameliorated glucose tolerance through suppression of oxidative stress and inflammation on fat in diabetic mice (2010)
  • Author(s): Ikeda Y, Tajima S, Yamano N, Kihira Y, Ishizawa K, Tomita S, Tsuchiya K, Tamaki T.
  • Organizer: American Heart Association Scientific Sessions 2010
  • Place of Presentation: Chicago, Illinois
  • Year and Date: 2010-11-04
• [Presentation] Deferoxamine, an iron chelator, enhances angiogenesis through Akt-eNOS pathway in endothelial cells (2010)
  • Author(s): Ikeda Y, Tajima S, Yamano N, Kihira Y, Ishizawa K, Tomita S, Tsuchiya K, Tamaki T.
  • Organizer: American Heart Association Scientific Sessions 2010
  • Place of Presentation: Chicago, Illinois
  • Year and Date: 2010-11-04
• [Presentation] Global gene expression analyses in renal ischemia-reperfusion injury(IRI) from mice lucking Hif-1a gene (2010)
  • Author(s): Tamaki T, Yamaguchi K, Kihira Y, Ikeda Y, Ishizawa K, TsuchiyaK, Kondo S, Kagami S and Tomita S
  • Organizer: Annual meeting for American Society of Nephrology
  • Place of Presentation: Colorado
  • Year and Date: 2010-09-18
• [Presentation] Deferoxamine, an iron chelator, promotes angiogenesis after ischemic hind limb through Akt-eNOS-dependent pathway (2010)
  • Author(s): Tajima S, Ikeda Y, Kihira Y, Ishizawa K, Kawazoe K, Tomita S, Minakuchi K, Tamaki T, Tsuchiya K
  • Organizer: The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto, June
  • Year and Date: 2010-07-14
• [Presentation] Amelioration of acute tubular necrosis in ischemic acute renal failure was impaired in mice lacking hypoxia inducible factor-1 gene (2010)
  • Author(s): Tamaki T, Yamaguchi K, Kihira Y, Ikeda Y, Ishizawa K, Tsuchiya K, Tomita S.
  • Organizer: International Society of Nephrology Nexus symposium 2010
  • Place of Presentation: Kyoto
  • Year and Date: 2010-05-18
• [Presentation] Deferoxamine, an iron chelator, promotes angiogenesis after ischemic hind limb through Akt-eNOS-dependent pathway (2010)
  • Author(s): Ikeda Y, Kihira Y, Ishizawa K, Tomita S, Tsuchiya K, Tamaki T
  • Organizer: XX World Congress ISHR 2010 KYOTO
  • Place of Presentation: Kyoto
  • Year and Date: 2010-05-14
• [Presentation] Role of HIF-1b in endothelial cells in monocrotalineinduced pulmonary hypertension in mice (2010)
  • Author(s): Fukuhara Y, Tomita S, Imamura Y, Horinouchi Y, Imanishi M, Sakurada T, Kitagawa T, Tamaki T
  • Organizer: The 16th World Congress of Basic and Clinical Pharmacology WorldPharma 2010
  • Place of Presentation: Copenhagen
  • Year and Date: 2010-03-14
• [Presentation] Basic fibroblast growth factor upregulates hypoxia inducible factor 1 and glucose transporter 1 in adipose cells (2010)
  • Author(s): Kihira Y, Tomita S, Ikeda Y, Ishizawa K, Tsuchiya K and Tamaki T
  • Organizer: The 16th World Congress of Basic and Clinical Pharmacology WorldPharma 2010
  • Place of Presentation: Copenhagen
  • Year and Date: 2010-03-14
• [Book] アンジオテンシンII刺激による細胞内遊離鉄を介した酸化ストレス増強機構 (2010)
  • Author(s): 田島壮一郎, 土屋浩一郎, 濱本磨以, 久住祥子, 堀ノ内裕也, 八木祐子, 櫻田巧, 石澤啓介, 池田康将, 木平孝高, 冨田修平, 玉置俊晃
  • Total Pages: 59-63
  • Publisher: 腎とフリーラジカル
• [Remarks] ホームページURL:
  • URL: http://150.59.76.31/university/servlet/index? & level=4 & reference=0/10001/3/30005/20012