High-density lipoproteins induce transforming growth factor- β2 expression in endothelial cells

Giuseppe Danilo Norata, Elisa Callegari, Marta Marchesi, Giulia Chiesa, Per Eriksson, Alberico L. Catapano

Research output: Contribution to journalArticlepeer-review

Abstract

Background - HDL is endowed with cardiovascular protective activities. In addition to its role in reverse cholesterol transport, HDL influences different functions of endothelial cells. In the present study, we investigated in endothelial cells the genes involved in inflammation modulated by HDL. Methods and Results - Through cDNA array analysis, transforming growth factor (TGF)-β2 appeared to be a gene responsive to HDL treatment in endothelial cells. Quantitative real-time polymerase chain reaction confirmed that HDL subfraction 3 selectively induces TGF-β, mRNA expression and protein release, whereas TGF-β1 and TGF-β3 were not affected. This effect was mainly PI3K/Akt dependent. Lysosphingolipids present in HDL such as sphingosine 1 phosphate and sphingosylphosphorylcholine mimicked the effects of the whole HDL. These results were confirmed in vivo in transgenic mice overexpressing human apolipoprotein (apo) A-I. Compared with apoA-I-knockout mice, phospho-Akt, phospho-ERK1/2, and TGF-β2 expression was increased in the aorta of transgenic mice overexpressing human apoA-I. In addition, the expression of phospho-Smad2/3, the transcription factor activated by TGF-β, is increased in transgenic mice compared with knockout mice. Conclusions - Because TGF-β possesses antiinflammatory properties and stabilizes the plaque, the results of the present work suggest a novel target for the antiatherosclerotic effect of HDL.

Original languageEnglish
Pages (from-to)2805-2811
Number of pages7
JournalCirculation
Volume111
Issue number21
DOIs
Publication statusPublished - May 31 2005

Keywords

  • Apolipoproteins
  • Endothelium
  • Lipoproteins
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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