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The transcription factor MEF2C negatively controls angiogenic sprouting of endothelial cells depending on oxygen

Caterina Sturtzel1, Julia Testori1, Bernhard Schweighofer1

  • 1Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.

Plos One
|July 3, 2014
PubMed

Insights

MEF2C transcription factor inhibits endothelial cell sprouting by upregulating alpha-2-macroglobulin. This MEF2C/alpha-2-macroglobulin axis acts as a negative feedback to regulate angiogenesis based on oxygen levels.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Physiology

Background:

  • Endothelial cells form new blood vessels through angiogenesis.
  • Vascular Endothelial Growth Factor-A (VEGF-A) and basic Fibroblast Growth Factor (bFGF) are key regulators of angiogenesis.
  • MEF2C is a MADS box transcription factor found in endothelial cells.

Purpose of the Study:

  • To investigate the role of MEF2C in angiogenesis.
  • To identify downstream targets of MEF2C in endothelial cells.
  • To elucidate the regulatory mechanism of MEF2C in response to angiogenic factors and oxygen levels.

Main Methods:

  • Gene expression profiling to identify MEF2C-regulated genes.
  • Overexpression and dominant-negative mutant studies of MEF2C in endothelial cells.
  • Alpha-2-macroglobulin knockdown using lentiviral shRNA.
  • Assessment of angiogenic sprouting and cell migration.
  • Hypoxia experiments to study gene regulation under low oxygen conditions.

Main Results:

  • MEF2C was upregulated by VEGF-A and bFGF in endothelial cells.
  • MEF2C significantly inhibited angiogenic sprouting, primarily by affecting cell migration, not proliferation.
  • MEF2C strongly induced the expression and secretion of alpha-2-macroglobulin.
  • Alpha-2-macroglobulin mediated the inhibitory effects of MEF2C on sprouting.
  • Hypoxia reduced MEF2C upregulation and alpha-2-macroglobulin production, diminishing the inhibitory effect.

Conclusions:

  • The MEF2C/alpha-2-macroglobulin axis serves as a negative feedback mechanism in endothelial cells.
  • This pathway regulates sprouting activity in response to oxygen concentration.
  • It plays a crucial role in preventing inappropriate and excessive angiogenesis.

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