Abstract
Macrophage uptake of oxidized low-density lipoprotein (oxLDL) is thought to play a central role in foam cell formation and the pathogenesis of atherosclerosis. We demonstrate here that oxLDL activates PPARγ-dependent transcription through a novel signaling pathway involving scavenger receptor- mediated particle uptake. Moreover, we identify two of the major oxidized lipid components of oxLDL, 9-HODE and 13-HODE, as endogenous activators and ligands of PPARγ. Our data suggest that the biologic effects of oxLDL are coordinated by two sets of receptors, one on the cell surface, which binds and internalizes the particle, and one in the nucleus, which is transcriptionally activated by its component lipids. These results suggest that PPARγ may be a key regulator of foam cell gene expression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 229-240 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 93 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 17 1998 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ. / Nagy, Laszlo; Tontonoz, Peter; Alvarez, Jacqueline G A; Chen, Hongwu; Evans, Ronald M.
In: Cell, Vol. 93, No. 2, 17.04.1998, p. 229-240.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ
AU - Nagy, Laszlo
AU - Tontonoz, Peter
AU - Alvarez, Jacqueline G A
AU - Chen, Hongwu
AU - Evans, Ronald M.
PY - 1998/4/17
Y1 - 1998/4/17
N2 - Macrophage uptake of oxidized low-density lipoprotein (oxLDL) is thought to play a central role in foam cell formation and the pathogenesis of atherosclerosis. We demonstrate here that oxLDL activates PPARγ-dependent transcription through a novel signaling pathway involving scavenger receptor- mediated particle uptake. Moreover, we identify two of the major oxidized lipid components of oxLDL, 9-HODE and 13-HODE, as endogenous activators and ligands of PPARγ. Our data suggest that the biologic effects of oxLDL are coordinated by two sets of receptors, one on the cell surface, which binds and internalizes the particle, and one in the nucleus, which is transcriptionally activated by its component lipids. These results suggest that PPARγ may be a key regulator of foam cell gene expression.
AB - Macrophage uptake of oxidized low-density lipoprotein (oxLDL) is thought to play a central role in foam cell formation and the pathogenesis of atherosclerosis. We demonstrate here that oxLDL activates PPARγ-dependent transcription through a novel signaling pathway involving scavenger receptor- mediated particle uptake. Moreover, we identify two of the major oxidized lipid components of oxLDL, 9-HODE and 13-HODE, as endogenous activators and ligands of PPARγ. Our data suggest that the biologic effects of oxLDL are coordinated by two sets of receptors, one on the cell surface, which binds and internalizes the particle, and one in the nucleus, which is transcriptionally activated by its component lipids. These results suggest that PPARγ may be a key regulator of foam cell gene expression.
UR - http://www.scopus.com/inward/record.url?scp=0032540325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032540325&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81574-3
DO - 10.1016/S0092-8674(00)81574-3
M3 - Article
C2 - 9568715
AN - SCOPUS:0032540325
VL - 93
SP - 229
EP - 240
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -