Lectin-like oxidized low-density lipoprotein receptor-1 regulates autophagy and Toll-like receptor 4 in the brain of hypertensive mice.
J Hypertens
; 33(3): 525-33; discussion 533, 2015 Mar.
Article
en En
| MEDLINE
| ID: mdl-25380158
ABSTRACT
BACKGROUND:
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) regulates blood pressure and is important for the development of inflammation, oxidative stress and autophagy. We posited that LOX-1 via NADPH oxidase activation may affect autophagy and Toll-like receptor (TLR)4 expression in the brains of hypertensive mice.METHODS:
To examine this postulate, wild-type mice were given continuous infusion of angiotensin II (50âng/min) for 28 days. As expected, these mice developed significant increase in blood pressure.RESULTS:
Corpus callosum in the brains of these hypertensive mice revealed intense expression of NADPH oxidase (subunits P22phox and P47phox), activation of P38 MAPK and nuclear factor-kappaB (P65), autophagy-related proteins (beclin-1 and conversion of LC3-I to LC3-II), and TLR4 (and associated signaling molecules myeloid differentiation primary response gene (88) and TIR-domain-containing adapter-inducing interferon-ß). These observations suggested activation of redox signals, autophagy and immune system. In parallel experiments, mice with LOX-1 deletion given similar infusion of angiotensin II showed much less expression of NADPH oxidase, activation of P38 MAPK and nuclear factor-kappaB, autophagy-related proteins and TLR4 [and myeloid differentiation primary response gene (88) and TIR-domain-containing adapter-inducing interferon-ß]. Mice with LOX-1 deletion also showed a smaller rise in blood pressure than wild-type mice, both groups given similar infusion of angiotensin II.CONCLUSION:
These studies suggest immune activation in the brains of mice with angiotensin II-induced hypertension. Further, these observations imply the existence of a link between LOX-1, NADPH oxidase expression, development of autophagy and immune activation in hypertension.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
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Encéfalo
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Receptor Toll-Like 4
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Receptores Depuradores de Clase E
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Hipertensión
Límite:
Animals
Idioma:
En
Revista:
J Hypertens
Año:
2015
Tipo del documento:
Article