期刊
JOURNAL OF HYPERTENSION
卷 33, 期 3, 页码 525-533出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0000000000000411
关键词
autophagy; hypertension; lectin-like oxidized low-density lipoprotein receptor-1; reactive oxygen species; Toll-like receptor 4
资金
- National Natural Science Foundation of China [31170904, 11228205, 61190123]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20121102110031]
- Department of Veterans Affairs, Washington, DC
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 (50 ng/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 P22(phox) and P47(phox)), 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-beta). 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-beta]. 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.
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