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Inhibitors of differentiation/DNA binding proteins Id1 and Id3 are regulated by statins in endothelial cells

J Pammer1, C Reinisch, C Kaun

  • 1Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria.

Endothelium : Journal of Endothelial Cell Research
|September 17, 2004
PubMed

Insights

Statins like fluvastatin up-regulate Id1 and down-regulate p53 in endothelial cells, potentially explaining their proangiogenic effects. This study investigates Id protein regulation in human dermal microvascular endothelial cells.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Id proteins (inhibitors of differentiation) regulate cell cycle, differentiation, and senescence.
  • Id proteins are implicated in angiogenesis, the formation of new blood vessels.
  • The effect of statins on Id protein regulation in endothelial cells is largely unknown.

Purpose of the Study:

  • To investigate the regulation of Id proteins (Id1, Id3) and related cell cycle regulators (p53, p21, p27) in endothelial cells by fluvastatin.
  • To determine the role of the AKT pathway in statin-mediated Id protein regulation.

Main Methods:

  • Human dermal microvascular endothelial cells (HDMECs) were treated with fluvastatin, VEGF, HGF, and serum in vitro.
  • Western blotting was used to analyze the expression of Id1, Id3, p53, p21, p27, and phosphorylated AKT.

Main Results:

  • Fluvastatin and serum up-regulated Id1 expression in HDMECs.
  • Fluvastatin slightly down-regulated Id3 and p53, but did not affect p21 or p27.
  • Fluvastatin did not induce AKT phosphorylation, unlike VEGF and HGF, suggesting this pathway is not involved in fluvastatin's effect on Id1.

Conclusions:

  • Statin treatment, specifically fluvastatin, can up-regulate Id1 and down-regulate p53 in endothelial cells.
  • These regulatory changes in Id proteins and p53 may contribute to the proangiogenic properties of statins.

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