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)-beta2 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-beta2 mRNA expression and protein release, whereas TGF-beta1 and TGF-beta3 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-beta2 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-beta, is increased in transgenic mice compared with knockout mice. CONCLUSIONS: Because TGF-beta possesses antiinflammatory properties and stabilizes the plaque, the results of the present work suggest a novel target for the antiatherosclerotic effect of HDL.
High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells / G.D. Norata, E. Callegari, M. Marchesi, G. Chiesa, P. Eriksson, A.L. Catapano. - In: CIRCULATION. - ISSN 0009-7322. - 111:21(2005), pp. 2805-2811.
|Titolo:||High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells|
NORATA, GIUSEPPE DANILO (Primo)
CALLEGARI, ELISA (Secondo)
CATAPANO, ALBERICO LUIGI (Ultimo)
|Parole Chiave:||Apolipoproteins; Endothelium; Lipoproteins; Signal transduction|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1161/CIRCULATIONAHA.104.472886|
|Appare nelle tipologie:||01 - Articolo su periodico|