Increased oxidized low-density lipoprotein causes blood-brain barrier disruption in early-onset preeclampsia through LOX-1.
FASEB J
; 27(3): 1254-63, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23230281
ABSTRACT
Early-onset preeclampsia (EPE) is a severe form of preeclampsia that involves life-threatening neurological complications. However, the underlying mechanism by which EPE affects the maternal brain is not known. We hypothesized that plasma from women with EPE increases blood-brain barrier (BBB) permeability vs. plasma from women with late-onset preeclampsia (LPE) or normal pregnancy (NP) and investigated its underlying mechanism by perfusing cerebral veins from nonpregnant rats (n=6-7/group) with human plasma from women with EPE, LPE, or NP and measuring permeability. We show that plasma from women with EPE significantly increased BBB permeability vs. plasma from women with LPE or NP (P<0.001). BBB disruption in response to EPE plasma was due to a 260% increase of circulating oxidized LDL (oxLDL) binding to its receptor, LOX-1, and subsequent generation of peroxynitrite (P<0.001). A rat model with pathologically high lipid levels in pregnancy showed symptoms of preeclampsia, including elevated blood pressure, growth-restricted fetuses, and LOX-1-dependent BBB disruption, similar to EPE (P<0.05). Thus, we have identified LOX-1 activation by oxLDL and subsequent peroxynitrite generation as a novel mechanism by which disruption of the BBB occurs in EPE. As increased BBB permeability is a primary means by which seizure and other neurological symptoms ensue, our findings highlight oxLDL, LOX-1, and peroxynitrite as important therapeutic targets in EPE.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pré-Eclâmpsia
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Terceiro Trimestre da Gravidez
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Permeabilidade Capilar
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Barreira Hematoencefálica
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Circulação Cerebrovascular
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Receptores Depuradores Classe E
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Lipoproteínas LDL
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article