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

Wuttge, Dirk LU ; Romert, A; Eriksson, U; Torma, H; Hansson, G K and Sirsjo, A (2001) In FASEB Journal 15(7). p.1221-1223
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
retinoic acid receptor, oxidized low-density lipoprotein, CD36, atherosclerosis, all-trans retinoic acid
in
FASEB Journal
volume
15
issue
7
pages
1221 - 1223
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • pmid:11344094
  • scopus:0035347298
ISSN
1530-6860
DOI
10.1096/fj.00-0488fje
language
English
LU publication?
no
id
7f70d1fb-f564-44d9-926a-64f96c1cfe61 (old id 1121864)
date added to LUP
2008-07-18 15:51:54
date last changed
2018-02-04 04:05:23
@article{7f70d1fb-f564-44d9-926a-64f96c1cfe61,
  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.},
  author       = {Wuttge, Dirk and Romert, A and Eriksson, U and Torma, H and Hansson, G K and Sirsjo, A},
  issn         = {1530-6860},
  keyword      = {retinoic acid receptor,oxidized low-density lipoprotein,CD36,atherosclerosis,all-trans retinoic acid},
  language     = {eng},
  number       = {7},
  pages        = {1221--1223},
  publisher    = {The Federation of American Societies for Experimental Biology},
  series       = {FASEB Journal},
  title        = {Induction of CD36 by all-trans retinoic acid: retinoic acid receptor signaling in the pathogenesis of atherosclerosis},
  url          = {http://dx.doi.org/10.1096/fj.00-0488fje},
  volume       = {15},
  year         = {2001},
}