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

转录辅因子PGC-1aIpha对内皮迁移和血管生成的调节

• 批准号: 22590825
• 负责人: SAWADA Naoki
• 金额: $ 2.91万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590825/
• 关键词: 分子血管病態学; 血管新生; 転写コアクチベータ

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.

严重的肢体缺血是导致截肢的主要原因，10-15%的糖尿病患者受到影响，迫切需要开发有效的治疗手段。糖尿病肢体缺血的高患病率在很大程度上是由于糖尿病患者无法形成新的血管(称为血管生成的过程)来恢复缺血组织的血液供应。然而，FBR的潜在机制在很大程度上还没有确定。在本研究中，我们证明了糖尿病使内皮细胞转录共激活因子pGC-1α的丰度增加，从而使内皮细胞对血管生成因子无反应，从而导致糖尿病血管生成能力减弱。

项目成果

Glucose-independent persistence of PAI-1 gene expression and H3K4 tri-methylation in type 1 diabetic mouse endothelium: implication in metabolic memory.

• DOI: 10.1016/j.bbrc.2013.02.064
• 发表时间: 2013-03
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Fumihiko Takizawa;S. Mizutani;Yoshihiro Ogawa;N. Sawada

Endothelial PGC-1alpha mediates vascular dysfunction in diabetes

内皮 PGC-1α 介导糖尿病血管功能障碍

• 发表时间: 2013
• 作者: 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
• 通讯作者: Zolt Arany

Endothelial PGC-1alpha mediates vascular dysfunction in diabetes.

内皮 PGC-1α 介导糖尿病血管功能障碍。

• 发表时间: 2013
• 作者: 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;大関敦子,渡辺昌文,真鍋一郎,王国琴,渡邉綾,河原崎秀一,山内敏正,原一雄,門脇孝,永井良三;澤田直樹（代表者)
• 通讯作者: 澤田直樹（代表者)