Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Medicine / 醫學院
  3. School of Medicine / 醫學系
  4. Electronegative LDL impairs vascular endothelial cell integrity in diabetes by disrupting fibroblast growth factor 2 (FGF2) autoregulation
 
  • Details

Electronegative LDL impairs vascular endothelial cell integrity in diabetes by disrupting fibroblast growth factor 2 (FGF2) autoregulation

Journal
Diabetes
Journal Volume
57
Journal Issue
1
Pages
158-166
Date Issued
2008
Author(s)
Lu J.
Jiang W.
Yang J.-H.
PO-YUAN CHANG  
Walterscheid J.P.
Chen H.-H.
Marcelli M.
Tang D.
Lee Y.-T.
Liao W.S.L.
Yang C.-Y.
Chen C.-H.
DOI
10.2337/db07-1287
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-38449095405&doi=10.2337%2fdb07-1287&partnerID=40&md5=15a482bfed8ba6de3d436dd5b008d984
https://scholars.lib.ntu.edu.tw/handle/123456789/533889
Abstract
OBJECTIVE - L5, a circulating electronegative LDL identified in patients with hypercholesterolemia or type 2 diabetes, induces endothelial cell (EC) apoptosis by suppressing fibroblast growth factor (FGF)2 expression. FGF2 plays a pivotal role in endothelial regeneration and compensatory arteriogenesis. It is likely that vasculopathy and poor collateralization in diabetes is a result of FGF2 dysregulation. RESEARCH DESIGN AND METHODS - To investigate this mechanism, we isolated L5 from type 2 diabetic patients. In cultured bovine aortic ECs (BAECs), L5 inhibited FGF2 transcription and induced apoptosis. Because FGF2 stimulates the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, we examined whether FGF2 transcription is regulated by Akt through a feedback mechanism. RESULTS - Diabetic L5 reduced FGF2 release to the medium but enhanced caspase-3 activity, with resultant apoptosis. Inhibition of PI3K with wortmannin or suppression of Akt activation with dominant-negative Akt inhibited FGF2 expression. Transfection of BAECs with FGF2 antisense cDNA depleted endogenous FGF2 protein. In these cells, not only was Akt phosphorylation inhibited, but FGF2 transcription was also critically impaired. In contrast, transfecting BAECs with FGF2 sense cDNA augmented Akt phosphorylation. Treatment with constitutively active Akt enhanced FGF2 expression. Augmentation of either FGF2 transcription or Akt phosphorylation rendered BAECs resistant to L5. CONCLUSIONS - These findings suggest that FGF2 is the primary initiator of its own expression, which is autoregulated through a novel FGF2-PI3K-Akt loop. Thus, by disrupting FGF2 autoregulation in vascular ECs, L5 may impair reendothelialization and collateralization in diabetes. ? 2008 by the American Diabetes Association.
SDGs

[SDGs]SDG3

Other Subjects
caspase 3; complementary DNA; fibroblast growth factor 2; low density lipoprotein; phosphatidylinositol 3 kinase; protein kinase B; vasculotropin; wortmannin; fibroblast growth factor 2; low density lipoprotein; oxidized low density lipoprotein; vasculotropin A; animal cell; article; autoregulation; cell culture; cell isolation; cell survival; controlled study; drug inhibition; enzyme activity; enzyme linked immunosorbent assay; gene control; genetic transcription; genetic transfection; human; human cell; non insulin dependent diabetes mellitus; nonhuman; Northern blotting; priority journal; protein expression; protein phosphorylation; vascular endothelium; Western blotting; animal; aorta; apoptosis; blood; cattle; cytology; drug effect; gene expression; homeostasis; isolation and purification; pathology; pathophysiology; physiology; reference value; vascular endothelium; Animals; Aorta; Apoptosis; Cattle; Diabetes Mellitus, Type 2; Endothelium, Vascular; Fibroblast Growth Factor 2; Gene Expression; Homeostasis; Humans; Lipoproteins, LDL; Reference Values; Vascular Endothelial Growth Factor A
Type
journal article

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science