The regulation of endothelial migration and angiogenesis by transcriptiona l coact I vator PGC-1aIpha

• Project/Area Number: 22590825
• 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: Tokyo Medical and Dental University
• Principal Investigator: SAWADA Naoki 東京医科歯科大学, 歯と骨のGCOE拠点, GCOE拠点形成特任教員 (40343751)
• Co-Investigator(Renkei-kenkyūsha): SATA Masataka 徳島大学, ヘルスバイオサイエンス研究, 教授 (80345214)
• Research Collaborator: ZOLT Arany Beth Israel Deaconess Medical Center, Harvard Medical School, Associate Professor of Medicine
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 分子血管病態学 / 血管新生 / 転写コアクチベータ

Research Abstract

Critical limb ischemia, the leading cause oflimb amputation, affects 10-15%ofdiabetic population, thus calling for critical needs to develop effective therapeutic means. The high prevalence oflimb ischemia in diabetes is in significant part caused by the inability of diabetics to elaborate new blood vessels (the process called angiogenesis) to resume blood supply in ischemic tissues. However, the underlying mechanism fbr this has been largely undefined. In the present study, we demonstrated that diabetes increases the abundance oftranscriptional co-activator PGC-1αin endothelial cells, which then renders endothelial cells unresponsive to angiogenic factors, and causes diminished angiogenic capacity in diabetes.

Research Products

• [Journal Article] Rho/Rho-Associated Coiled-Coil Forming Kinase Pathway as Therapeutic Targets for Statins in Atherosclerosis (2013)
  • Author(s): Sawada N, Liao JK
  • Journal Title: Antioxid Redox Signal Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Glucose-independent persistence of PAl-1 gene expression and H3K4 tri-methylation in type 1 diabetic mouse endothelium; lmplication in metabolic memory (2013)
  • Author(s): Takizawa F, Mizutani S, Ogawa Y Sawada N
  • Journal Title: Biochem Biophys Res Commun Volume: 433(1) Pages: 66-72
  • Peer Reviewed
• [Journal Article] Glucose-independent persistence of PAI-1 gene expression and H3K4 tri-methylation in type 1 diabetic mouse endothelium: implication in metabolic memory. (2013)
  • Author(s): Takizawa F, Mizutani S, Ogawa Y, Sawada N.
  • Journal Title: Biochem Biophys Res Commun. Volume: 433(1) Issue: 1 Pages: 66-72
  • DOI: 10.1016/j.bbrc.2013.02.064
  • Peer Reviewed
• [Journal Article] Role of transient receptor potential vanilloid 2 in LPS-induced cytokine production in macrophages (2010)
  • Author(s): Yamashiro K, Sasano T, Tbjo K, Namekata l, Kurokawa J, Sawada N, Suganami T, Kamei Y Tanaka H,Tajima N, Utsunomiya K, Ogawa Y Furukawa T
  • Journal Title: Biochem Biophys Res Commun Volume: 398(2) Pages: 284-289
  • Peer Reviewed
• [Journal Article] Endothelial PGC-1α mediates vascular dysfunction in diabetes
  • Author(s): Sawada N, Jiang A, Takizawa F, Safdar A, Manika A, Tesmenitsky Y, Kang K-T, Bischoff J, Kalwa H, Sartoretto J, Kamei Y, Benjamin LE, Watada H, Ogawa Y, Higashikuni Y, Kessinger CW, Jaffer FA, Michel T, Sata M, Croce K, Tanaka R, Arany Z
  • Journal Title: Cell Metab Volume: (in press)
  • Peer Reviewed
• [Presentation] Endothelial PGC-1alpha mediates vascular dysfunction in diabetes (2013)
  • Author(s): Fumihiko Takizawa, Naoki Sawada, Aihua Jiang, Kevin Croce, Andre Manika, Yevgenia Tesmenitsky, Kyu Tae Kang, Joyce Bischoff, Hermann Kalwa, Thomas Michel, Laura E. Benjamin, Masataka Sata, Zolt Arany
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2013-03-16
• [Presentation] Endothelial PGC-1alpha mediates vascular dysfunction in diabetes (2013)
  • Author(s): Naoki Sawada, Aihua Jiang, Fumihiko Takizawa, Kevin Croce, Andre Manika, Yevgenia Tesmenitsky, Kyu Tae Kang, Joyce Bischoff, Hermann Kalwa, Thomas Michel,Yasutomi Kamei, Laura E. Benjamin, Masataka Sata, Yoshihiro Ogawa, Zolt Arany
  • Organizer: The American Society for Clinical lnvestigation/Association of American Physicians Joint Meeting
  • Place of Presentation: Chicago, lllinois, USA
• [Presentation] Endothelial PGC-1alpha mediates vascular dysfunction in diabetes (2013)
  • Author(s): Naoki Sawada, Aihua Jiang, Fumihiko Takizawa, Kevin Croce, Andre Manika, Yevgenia Tesmenitsky, Kyu Tae Kang, Joyce Bischoff, Hermann Kalwa, Thomas Michel, Yasutomi Kamei, Laura E. Benjamin, Masataka Sata, Shuki Mizutani, Yoshihiro Ogawa, Zolt Arany
  • Organizer: Gordon Research Conference, Vascular Cell Biology
  • Place of Presentation: Ventura, California, USA
• [Presentation] Endothelial PGC-1alpha mediates vascular dysfunction in diabetes. (2013)
  • Author(s): 澤田直樹（代表者)
  • Organizer: The American Society for Clinical Investigation/Association of American Physicians Joint Meeting
  • Place of Presentation: Chicago, Illinois, USA
• [Presentation] Endothelial PGC-1alpha mediates vascular dysfunction in diabetes. (2013)
  • Author(s): 澤田直樹（代表者)
  • Organizer: Gordon Research Conference, Vascular Cell Biology
  • Place of Presentation: Ventura, California, USA
• [Presentation] Racl GTPase is a critical mediator of endothelium-derived neurotrophic activity (2012)
  • Author(s): Naoki Sawada, Ybshihiro Ogawa, James K. Liao
  • Organizer: Neuro-Vascular Wiring Sym posium 2012
  • Place of Presentation: Nara, Japan
• [Presentation] Endothelial PGC-1alpha mediates vascular dysfunction in diabetes (2012)
  • Author(s): Naoki Sawada, Aihua Jiang, Fumihiko Takizawa, Kevin Croce, Andre Manika, Yevgenia Tesmenitsky, Kyu Tae Kang, Joyce Bischoff, Hermann Kalwa, Thomas Michel, Yasutomi Kamei, Laura E. Benjamin, Masataka Sata, Shuki Mizutani, Yoshihiro Ogawa, Zolt Arany
  • Organizer: ATVB Early Career Investigator Award competition, American Heart Association Scientific Sessions 2012
  • Place of Presentation: Los Angeles, California, USA
• [Presentation] Rac1 GTPase is a critical mediator of endothelium-derived neurotrophic activity. (2012)
  • Author(s): Naoki Sawada, Yoshihiro Ogawa, James K. Liao.
  • Organizer: Neuro-Vascular Wiring Symposium 2012
  • Place of Presentation: 奈良市
• [Presentation] Endothelial PGC-1alpha mediates vascular dysfunction in diabetes. (2012)
  • Author(s): 澤田直樹（代表者)
  • Organizer: ATVB Early Career Investigator Award competition, American Heart Association Scientific Sessions 2012
  • Place of Presentation: Los Angeles, California, USA
• [Presentation] Endothelial PGC-1alpha is highly responsive to metabolic stress and serves as a key determinant of angiogenic response. Symposium' Young Scientist lnitiative Program (2011)
  • Author(s): Naoki Sawada, Aihua Jiang, Fumihiko Takizawa, Kevin Croce, Andre Manika, Yevgenia Tesmenitsky, Kyu Tae Kang, Joyce Bischoff, Hermann Kalwa, Thomas Michel, Yasutomi Kamei, Laura E. Benjamin, Masataka Sata, Shuki Mizutani, Yoshihiro Ogawa, Zolt Arany
  • Organizer: The 19th Scientific session. Japanese Vascular Biology and Medical Organization
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2011-12-09