Inhibiting Receptor of Advanced Glycation End Products Attenuates Pressure Overload-Induced Cardiac Dysfunction by Preventing Excessive Autophagy.
Inhibiting Receptor of Advanced Glycation End Products Attenuates Pressure Overload-Induced Cardiac Dysfunction by Preventing Excessive Autophagy.
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抑制晚期糖基化终产物受体可通过防止过度自噬来减轻压力过载引起的心脏功能障碍。
DOI：
10.3389/fphys.2018.01333
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发表时间：
2018
影响因子：
4
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Gao W;Zhou Z;Liang B;Huang Y;Yang Z;Chen Y;Zhang L;Yan C;Wang J;Lu L;Wen Z;Xian S;Wang L
晚期糖基化终产物受体(RAGE)通过介导多种病理过程参与心力衰竭(HF)，包括促进炎症和自噬。然而，RAGE在压力超负荷所致心力衰竭中的作用尚不清楚。我们发现，刺激RAGE可引起新生大鼠心室肌细胞(NRVMs)死亡，而ATG5基因敲除可减轻细胞死亡。以小鼠横断主动脉缩窄(TAC)为模型，在TAC后8周，我们证明RAGE基因敲除或RAGE阻断可减轻心肌肥大、纤维化和心功能不全。重要的是，RAGE基因敲除逆转了自噬相关蛋白(LC3BII/I和Beclin 1)的上调，并减少了心肌细胞的死亡，表明TAC后过度的自噬受到抑制。此外，RAGE基因敲除或阻断减少了介导自噬的pp65-NFκB和BNIP3的上调。综上所述，这些结果表明RAGE通过调节自噬在HF的进展中起着重要作用。因此，抑制RAGE-自噬轴可能是治疗心力衰竭的一种有前途的新策略。
The receptor for advanced glycation end products (RAGE) is involved in heart failure (HF) by mediating diverse pathologic processes, including the promotion of inflammation and autophagy. However, the role of RAGE in pressure overload-induced HF is not well understood. We found that stimulation of RAGE triggered the death of neonatal rat ventricular myocytes (NRVMs), while cell death was alleviated by ATG5 knockdown. Using transverse aortic constriction (TAC) in mice as a model of pressure overload-induced HF, we demonstrated that RAGE knockout or RAGE blockade attenuated cardiac hypertrophy and fibrosis as well as cardiac dysfunction at 8 weeks after TAC. Importantly, RAGE knockout reversed upregulation of autophagy related proteins (LC3BII/I and Beclin 1) and reduced cardiomyocyte death, indicating that excessive autophagy after TAC was inhibited. Moreover, RAGE knockout or blockade reduced the upregulation of pp65-NFκB and BNIP3, which mediate autophagy. Taken together, these results suggest that RAGE plays an important role in the progression of HF by regulating autophagy. Therefore, inhibition of the RAGE-autophagy axis could be a promising new strategy for treatment of heart failure.
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影响因子：
29
作者：
Singh R;Cuervo AM
通讯作者：
Cuervo AM
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
影响因子：
5
作者：
Liu, Yu;Yu, Manli;Zhao, Xianxian
通讯作者：
Zhao, Xianxian
影响因子：
18.2
作者：
Wang, Ling Jie;Lu, Lin;Shen, Wei Feng
通讯作者：
Shen, Wei Feng
DOI：
10.1073/pnas.0807735105
发表时间：
2008-12-30
影响因子：
11.1
作者：
Shaw, James;Zhang, Tong;Kirshenbaum, Lorrie A.
通讯作者：
Kirshenbaum, Lorrie A.
影响因子：
9.3
作者：
Hou X;Hu Z;Xu H;Xu J;Zhang S;Zhong Y;He X;Wang N
通讯作者：
Wang N