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Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption
09:20

Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption

Published on: October 4, 2019

High glucose-induced downregulation of connexin 43 expression promotes apoptosis in microvascular endothelial cells

An-Fei Li1, Sayon Roy

  • 1Department of Ophthalmology, University School of Medicine, Boston, Massachusetts 02118, USA.

Investigative Ophthalmology & Visual Science
|November 26, 2008
PubMed
Abstract

Insights

High glucose reduces connexin 43 (Cx43) expression and gap junction communication, triggering apoptosis in microvascular cells. This Cx43 downregulation is an early event in cell loss, potentially impacting diabetic retinopathy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • High glucose levels are implicated in microvascular complications.
  • Connexin 43 (Cx43) plays a crucial role in maintaining endothelial cell function and communication.
  • Gap junction intercellular communication (GJIC) is vital for vascular homeostasis.

Purpose of the Study:

  • To investigate if high glucose-induced inhibition of Cx43 expression and reduced GJIC promote microvascular endothelial cell loss.
  • To determine the role of Cx43 in high glucose-induced apoptosis of microvascular cells.

Main Methods:

  • Rat microvascular endothelial cells (RMECs) were cultured in high glucose (30 mM) or transfected with antisense-Cx43 (AS-Cx43) oligonucleotides to downregulate Cx43.
  • Cx43 protein expression was assessed by Western blot.
  • GJIC activity was measured using scrape load dye transfer (SLDT) assays.
  • Apoptosis was evaluated using DNA ladder assays, TUNEL assays, and differential staining.

Main Results:

  • Reduced Cx43 protein expression and GJIC activity were confirmed in high-glucose and AS-Cx43-treated cells.
  • A significant increase in apoptotic cells was observed when Cx43 expression was downregulated.
  • DNA fragmentation, indicative of early apoptosis, was evident in cells with reduced Cx43.

Conclusions:

  • High glucose-induced downregulation of Cx43 expression is an early trigger for apoptosis in microvascular endothelial cells.
  • This Cx43 downregulation and subsequent cell loss may contribute to vascular homeostasis breakdown and apoptosis initiation in diabetic retinopathy.

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