期刊
ATHEROSCLEROSIS
卷 261, 期 -, 页码 90-98出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2017.02.012
关键词
Angiotensin; Matrix metalloproteinase-8; Smooth muscle cell
资金
- National Natural Science Foundation of China (NSFC) [81400265, 81270274, 81470473, 81600340]
- Peking University People's Hospital Research and Development Funds [RDB2014-16]
Background and aims: Angiotensin II (Ang II) is a bioactive peptide that is related to cardiovascular disease such as atherosclerosis, whereas angiotensin-(1-7) (Ang-(1-7)) is a counter-regulator of angiotensin II, which protects against cardiovascular disease. Matrix metalloproteinase 8 (MMP-8) is thought to participate in plaque destabilization though degradation of extracellular matrix, improving the development of atherosclerosis. Whether Ang-(1-7) modulates Ang II-induced MMP-8 remains unclear. In this study, we investigated the effect of Ang-(1-7) on Ang II-induced MMP-8 expression in smooth muscle cells. Methods: Smooth muscle cells were treated with Ang II, Ang-(1-7) and their antagonists. In addition, ApoE knockout mice were fed a high fat diet and subcutaneously injected with Ang II, Ang-(1-7), Ang II+Ang-(1-7) (+/- A779). Results: We found that Ang II increased MMP-8 mRNA and protein expression in vascular smooth muscle cells, while Ang-(1-7) alone had no effect. However, Ang-(1-7) inhibited Ang II-induced MMP-8 expression. The inhibitory effect of Ang-(1-7) could be abolished by the competitive antagonist of Ang(1-7) at the MAS receptor. Furthermore, Ang II induced p38 MAPK activation, and this was inhibited by the treatment of Ang-(1-7). Ang II-induced MMP-8 expression could be attenuated by the p38 MAPK inhibitor SB203580. Ang-(1-7) also significantly suppressed Ang II-induced MMP-8 in both atherosclerotic plaques and serum in ApoE(-/)-mice. The atherosclerotic plaques in mice treated with Ang-(1-7) and Ang II appeared to be more stable with more type I collagen contents than those in mice treated with Ang II. Conclusions: Our results suggest that Ang-(1-7) plays an important role in protecting against atherosclerosis via counter-regulation of Ang II-induced MMP-8. (C) 2017 Elsevier B.V. All rights reserved.
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