Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress.
Cell Metab
; 12(5): 467-82, 2010 Nov 03.
Article
em En
| MEDLINE
| ID: mdl-21035758
ABSTRACT
Macrophage apoptosis in advanced atheromata, a key process in plaque necrosis, involves the combination of ER stress with other proapoptotic stimuli. We show here that oxidized phospholipids, oxidized LDL, saturated fatty acids (SFAs), and lipoprotein(a) trigger apoptosis in ER-stressed macrophages through a mechanism requiring both CD36 and Toll-like receptor 2 (TLR2). In vivo, macrophage apoptosis was induced in SFA-fed, ER-stressed wild-type but not Cd36â»(/)â» or Tlr2â»(/)â» mice. For atherosclerosis, we combined TLR2 deficiency with that of TLR4, which can also promote apoptosis in ER-stressed macrophages. Advanced lesions of fat-fed Ldlrâ»(/)â» mice transplanted with Tlr4â»(/)â»Tlr2â»(/)â» bone marrow were markedly protected from macrophage apoptosis and plaque necrosis compared with WT âLdlrâ»(/)â» lesions. These findings provide insight into how atherogenic lipoproteins trigger macrophage apoptosis in the setting of ER stress and how TLR activation might promote macrophage apoptosis and plaque necrosis in advanced atherosclerosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfolipídeos
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Apoptose
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Antígenos CD36
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Receptor 2 Toll-Like
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Ácidos Graxos
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Lipoproteínas
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Macrófagos
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article