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On-Chip Endothelial Inflammatory Phenotyping
12:43

On-Chip Endothelial Inflammatory Phenotyping

Published on: July 22, 2012

Gene expression profiling of inflamed human endothelial cells and influence of activated protein C

Nicola Franscini1, Esther B Bachli, Nenad Blau

  • 1Medical Clinic B Research Unit, Department of Medicine, University Hospital, Zürich, Switzerland.

Circulation
|October 27, 2004
PubMed

Insights

Activated protein C (APC) reduces inflammation in human coronary artery endothelial cells by downregulating key inflammatory genes. This pathway offers a novel anti-inflammatory mechanism, particularly effective in mild to moderate inflammation.

Area of Science:

  • Endothelial biology
  • Inflammation research
  • Coagulation and inflammation pathways

Background:

  • Systemic inflammation activates vascular endothelium, causing hypotension, thrombosis, and organ damage.
  • The activated protein C (APC) pathway links coagulation and inflammation.
  • Endothelial cells are central to inflammatory responses.

Purpose of the Study:

  • To investigate gene expression profiles in human coronary artery endothelial cells (HCAECs) stimulated with proinflammatory cytokines.
  • To determine the influence of APC on the expression of candidate genes regulated by these stimuli.

Main Methods:

  • Human coronary artery endothelial cells (HCAECs) were stimulated with interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha.
  • Gene expression profiling was performed, followed by verification using real-time PCR, ELISA, and HPLC.
  • Activities of transcription factors were assessed.

Main Results:

  • APC downregulated tetrahydrobiopterin (BH4) synthesis, interleukin-6, interleukin-8, monocyte chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) at transcriptional and protein levels.
  • APC inhibited the activities of transcription factors c-Fos, FosB, and c-Rel in inflamed HCAECs.
  • APC did not affect endothelial nitric oxide synthase, endothelial adhesion molecule, or vascular cell adhesion molecule-1.

Conclusions:

  • APC exhibits a novel anti-inflammatory mechanism in HCAECs by suppressing c-Fos-dependent induction of MCP-1 and ICAM-1.
  • APC downregulates the expression and activity of inflammation-related genes.
  • This effect is most pronounced under intermediate or mild inflammatory conditions.
Abstract

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