期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 791, 期 -, 页码 535-543出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2016.07.008
关键词
Receptor for advanced glycation end products; Transverse aortic constriction; Heart failure; AMPK/mTOR; NF kappa B
资金
- National Natural Science Foundation of China [81370266, 81400287, 81400358]
Heart failure is the consequence of sustained, abnormal neurohormonal and mechanical stress and remains a leading cause of death worldwide. The aim of this work was to identify whether blockade of receptor for advanced glycation end products (RAGE) protected against systolic overload -induced heart failure and investigate the possible underlying mechanism. It was found that RAGE mRNA and protein expression was up -regulated in cardiac tissues from mice subjected to pressure overload by transverse aortic constriction (TAC). Importantly, inhibition of RAGE by treatment with soluble RAGE (sRAGE) or FPS-ZM1 (a high -affinity RAGE -specific inhibitor) for 8 weeks attenuated cardiac remodeling (including cardiac hypertrophy and fibrosis), and dysfunction in mice exposed to TAC. Furthermore, treatment of TAC mice with sRAGE or FPS-ZM1 enhanced phosphorylation of AMPK and reduced phosphorylation of mTOR and protein expression of NF kappa B p65 in cardiac tissues. In addition, treatment of TAC mice with sRAGE or FPS-ZM1 abated oxidative stress, attenuated endoplasmic reticulum stress, and suppressed inflammation in cardiac tissues. These data demonstrated the benefits of blocking RAGE on the progression of systolic overload -induced heart failure in mice, which was possibly through modulating AMPK/mTOR and NF kappa B pathways. (C) 2016 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据