Immune complexes containing malondialdehyde (MDA) LDL induce apoptosis in human macrophages.
Clin Immunol
; 187: 1-9, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-28689783
ABSTRACT
Immune complexes (IC) containing predominantly malondialdehyde-LDL and the corresponding autoantibodies (MDA-LDL IC) predict acute cardiovascular events, while IC rich in oxidized LDL (oxLDL IC) predict cardiovascular disease progression. Our objective was to determine mechanisms that could explain these prognostic differences. We compared the effects of the interaction of oxLDL, MDA-LDL and the corresponding IC with human macrophages focusing on apoptosis, metalloproteinases, and proinflammatory cytokines. MDA-LDL IC induced higher degrees of apoptosis, higher levels of caspase-3 expression, and increased expression and release of MMP-1 and TNF compared to MDA-LDL, oxLDL, and oxLDL IC. The pro-apoptotic effects of MDA-LDL IC were inhibited by blocking TNFR 1 or FcγRI. Blocking FcγRI abrogated the induction and expression of MMPs and proinflammatory cytokines by MDA-LDL IC. In conclusion, the interaction of MDA-LDL IC with FcγRI triggers macrophage apoptosis and increased expression and release of TNF and MMP-1, which can lead to the rupture of unstable plaques.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Apoptose
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Aterosclerose
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Placa Aterosclerótica
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Lipoproteínas LDL
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Macrófagos
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Malondialdeído
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Complexo Antígeno-Anticorpo
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article