The bisphosphonate ibandronate stimulates reverse cholesterol transport out of monocytoid cells by enhanced ABCA1 transcription

Biochem Biophys Res Commun. 2003 Jul 18;307(1):23-30. doi: 10.1016/s0006-291x(03)01127-6.


Nitrogen-containing bisphosphonates used in osteoporosis act by interference with pyrophosphorylated intermediates of the sterol pathway and are internalized by monocytes/macrophages, key players in atherogenesis. We therefore studied the effects of ibandronate on monocytic cholesterol homeostasis. In differentiated human MM6 cells and freshly prepared human PBMCs lipoprotein receptor transcription was quantified by real-time RT-PCR and receptor-mediated cellular cholesterol handling by lipoprotein-driven uptake and efflux assays. Low nanomolar concentrations of ibandronate reduced cellular cholesterol content despite reactive up-regulation of the LDL receptor. Simultaneously, the transcription of the cellular cholesterol exporter ABCA1 was severalfold stimulated, whereas the scavenger receptor CD36 was down-regulated. Thereby, ibandronate decreased the cellular uptake of modified LDL and enhanced the efflux of cholesterol to delipidated HDL. Geranylgeraniol antagonized the stimulation of ABCA1 expression by ibandronate. Ibandronate in low pharmacologic concentrations redirects monocytic cholesterol handling from favouring foam cell formation towards enhanced reverse cholesterol transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Biological Transport / physiology*
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism
  • Cell Line
  • Cholesterol / metabolism*
  • Diphosphonates / pharmacology*
  • Homeostasis
  • Humans
  • Ibandronic Acid
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / chemistry
  • Lipoproteins, LDL / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Polyisoprenyl Phosphates / metabolism
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Transcription, Genetic*


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • CD36 Antigens
  • Diphosphonates
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Polyisoprenyl Phosphates
  • Receptors, LDL
  • Cholesterol
  • geranylgeranyl pyrophosphate
  • Ibandronic Acid