Influence of caveolin-1 on cellular cholesterol efflux mediated by high-density lipoproteins

Philippe G. Frank, Ferruccio Galbiati, Daniela Volonte, Babak Razani, David E. Cohen, Yves L. Marcel, Michael P. Lisanti

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Caveolin-1 is a principal structural component of caveolae membranes. These membrane microdomains participate in the regulation of signaling, transcytosis, and cholesterol homeostasis at the plasma membrane. In the present study, we determined the effect of caveolin-1 expression on cellular cholesterol efflux mediated by high-density lipoprotein (HDL). We evaluated this effect in parental NIH/3T3 cells as well as in two transformed NIH/3T3 cell lines in which caveolin-1 protein levels are dramatically downregulated. Compared with parental NIH/3T3 cells, these two transformed cell lines effluxed cholesterol more rapidly to HDL. In addition, NIH/3T3 cells harboring caveolin-1 antisense also effluxed cholesterol more rapidly to HDL. However, this effect was not due to changes in total cellular cholesterol content. We further showed that chronic HDL exposure reduced caveolin-1 protein expression in NIH/3T3 cells. HDL exposure also inhibited caveolin-1 promoter activity, suggesting a direct negative effect of HDL on caveolin-1 gene transcription. Moreover, we showed that HDL-induced downregulation of caveolin-1 prevents the uptake of oxidized low-density lipoprotein in human endothelial cells. These data suggest a novel proatherogenic role for caveolin-1, i.e., regarding the uptake and/or transcytosis of modified lipoproteins.

Original languageEnglish
Pages (from-to)C1204-C1214
JournalAmerican Journal of Physiology - Cell Physiology
Volume280
Issue number5 49-5
DOIs
StatePublished - 2001

Keywords

  • Caveolin
  • Oxidized low-density lipoprotein
  • Sterol regulatory element-binding proteins

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