Induction of CD36 by all-trans retinoic acid: retinoic acid receptor signaling in the pathogenesis of atherosclerosis

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Scavenger receptors mediating the uptake of oxidized low-density lipoproteins (oxLDL) by macrophages play a crucial role in foam cell formation during atherosclerosis. One member of this receptor family, the thrombospondin receptor CD36, has recently been shown to mediate a major part of the oxLDL-induced aggravation of atherosclerotic lesions. Here, we show that the expression of CD36 protein and mRNA in human monocytic THP-1 cells is increased by all-trans retinoic acid (atRA), a derivative of the essential Vitamin A, which leads to increased uptake of oxLDL. CD3106, a specific antagonist at the retinoic acid receptor (RAR), inhibited the atRA-induced CD36 expression, whereas the RAR-specific agonist CD367 induced CD36 to the same degree as atRA. This indicates an RAR-mediated CD36 induction. AtRA and oxLDL had synergistic effects in up-regulating CD36 when in both THP-1 cells and primary monocytes. Applying a sensitive RAR-GAL-4 reporter assay, we could demonstrate RAR ligands in human atherosclerotic lesions. In addition, immunohistochemistry showed RAR-a and -g in the lesions, which indicates that atRA may contribute to foam cell formation and the progress of atherosclerosis.

Detaljer

Författare
  • Dirk Wuttge
  • A Romert
  • U Eriksson
  • H Torma
  • G K Hansson
  • A Sirsjo
Externa organisationer
  • External Organization - Unknown
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)1221-1223
TidskriftFASEB Journal
Volym15
Utgåva nummer7
StatusPublished - 2001
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa