Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Diabetic LDL inhibits cell-cycle progression via STAT5B and p21waf
Maria Felice Brizzi, … , Gianfranco Pagano, Luigi Pegoraro
Maria Felice Brizzi, … , Gianfranco Pagano, Luigi Pegoraro
Published January 1, 2002
Citation Information: J Clin Invest. 2002;109(1):111-119. https://doi.org/10.1172/JCI13617.
View: Text | PDF
Article Article has an altmetric score of 4

Diabetic LDL inhibits cell-cycle progression via STAT5B and p21waf

  • Text
  • PDF
Abstract

Modified LDL is a major cause of injury to the endothelium in diabetes. In the present study, we analyzed the effects on endothelial cells of LDL recovered from type 2 diabetic patients (dm-LDL) or from nondiabetic subjects (n-LDL). Treatment of human umbilical vein endothelial cells with dm-LDL, but not n-LDL, led to the accumulation of cells in G1. To dissect the molecular mechanisms of this effect, we analyzed the expression and function of the cyclin-dependent kinase inhibitor p21waf, a cell cycle regulator known to be a target of the signal transducers and activators of transcription (STATs). dm-LDL led to transient STAT5 phosphorylation and the formation of a STAT5-containing complex and activated p21waf expression at the transcriptional level. Expression of the dominant-negative form of STAT5B, but not of STAT5A, significantly decreased both p21waf expression and the fraction of cells in G1. Finally, immunofluorescence analysis demonstrated that activated STAT5 is expressed in newly formed intraplaque vessels and in endothelial cells lining the luminal side of the plaque. Similarly, p21waf immunoreactivity was found in the neointimal vasculature. Our results suggest a role of STAT5B as a regulator of gene expression in diabetes-associated vascular disease.

Authors

Maria Felice Brizzi, Patrizia Dentelli, Marzia Pavan, Arturo Rosso, Roberto Gambino, Maria Grazia De Cesaris, Giovanni Garbarino, Giovanni Camussi, Gianfranco Pagano, Luigi Pegoraro

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
dm-LDL increases p21waf expression via a transcriptional mechanism. (a) ...
dm-LDL increases p21waf expression via a transcriptional mechanism. (a) p21waf and p27kip1 expression. Proteins from lysed HUVECs were incubated with n-LDL or dm-LDL for different time periods, subjected to 15% SDS-PAGE, and electrophoretically transferred to nitrocellulose filters. The filters were immunoblotted with an anti-p21waf antibody or an anti-p27kip1 antiserum. Five different experiments were performed with similar results. (b) p21waf gene transcription. RNAs were obtained from nuclei prepared from unstimulated HUVECs or HUVECs stimulated with dm-LDL for 90 minutes. Equal cpm of the purified radioactive RNAs from the respective reactions were hybridized against p21waf and β-actin cDNAs dot-blotted on the same filter. Similar results were obtained in two different experiments. (c) n-LDL does not compete with dm-LDL. HUVECs were unstimulated (lane 1) or were stimulated for 18 hours with dm-LDL alone (lane 2) or in combination with n-LDL (50- and 100-fold excess, lanes 3 and 4, respectively), and evaluated for p21waf as above. Similar results were obtained in three different experiments. IB, immunoblot.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 1 patents
Mentioned by 1 peer review sites
1 readers on Mendeley
See more details