Blockade of receptor for advanced glycation end products protects against systolic overload-induced heart failure after transverse aortic constriction in mice
Blockade of receptor for advanced glycation end products protects against systolic overload-induced heart failure after transverse aortic constriction in mice
复制标题
阻断晚期糖基化终末产物受体可预防小鼠横主动脉缩窄后收缩超负荷诱发的心力衰竭
DOI：
10.1016/j.ejphar.2016.07.008
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发表时间：
2016-11-15
影响因子：
5
通讯作者：
Zhao, Xianxian
中科院分区：
文献类型：
--
作者：
Liu, Yu;Yu, Manli;Zhao, Xianxian
心力衰竭是持续的、异常的神经激素和机械应激的结果，并且仍然是全世界死亡的主要原因。本研究的目的是确定阻断晚期糖基化终末产物受体（receptor for advanced glycation end products，RECEPTOR）是否能预防收缩超负荷诱导的心力衰竭，并探讨其可能的机制。结果发现，在横主动脉缩窄（TAC）压力超负荷的小鼠心肌组织中，BMPmRNA和蛋白表达上调。重要的是，在暴露于TAC的小鼠中，通过用可溶性β-淀粉样蛋白（saponin）或FPS-ZM 1（高亲和力β-淀粉样蛋白特异性抑制剂）治疗8周来抑制β-淀粉样蛋白减弱心脏重塑（包括心脏肥大和纤维化）和功能障碍。此外，用sodium或FPS-ZM 1处理TAC小鼠增强AMPK的磷酸化，并降低mTOR的磷酸化和心脏组织中NF κ B p65的蛋白表达。此外，用sodium或FPS-ZM 1治疗TAC小鼠减轻了氧化应激，减弱了内质网应激，并抑制了心脏组织中的炎症。这些数据证明阻断AMPK对小鼠中收缩超负荷诱导的心力衰竭的进展的益处，这可能是通过调节AMPK/mTOR和NF κ B途径。(C)2016爱思唯尔B. V.保留所有权利。
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.