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Front. Physiol. | doi: 10.3389/fphys.2018.01333

Inhibiting Receptor of Advanced Glycation End Products Attenuates Pressure Overload-induced Cardiac Dysfunction by Preventing Excessive Autophagy

 Wenbin Gao1, 2,  Zheng Zhou1, 2,  Birong Liang1, 2,  Yusheng Huang1, 2, Zhongqi Yang1, 2,  Yang Chen2, 3,  Lu Zhang1, 2,  Cui Yan1, 2, Jiajia Wang1, 2,  Lu Lu1, 2,  Zhaorui Wen2,  Shaoxiang Xian1, 2* and  Lingjun Wang1, 2*
  • 1The First Affiliated Hospital, Guangzhou University of Chinese Medicine, China
  • 2Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, China
  • 3School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, China

The receptor for advanced glycation end products (RAGE) is involved in heart failure by mediating diverse pathologic processes, including the promotion of inflammation and autophagy. However, the role of RAGE in pressure overload-induced heart failure 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 heart failure, 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-NFĸB and BNIP3, which mediate autophagy. Taken together, these results suggest that RAGE plays an important role in the progression of heart failure by regulating autophagy. Therefore, inhibition of the RAGE-autophagy axis could be a promising new strategy for treatment of heart failure.

Keywords: receptor of advanced glycation end-products, Autophagy, Cardiac dysfunction, Autophagic cell death, cardiac hypertrophy

Received: 27 Feb 2018; Accepted: 04 Sep 2018.

Edited by:

Anna M. Watson, Monash University, Australia

Reviewed by:

Francisco Altamirano, University of Texas Southwestern Medical Center, United States
Zhao Wang, University of Texas Southwestern Medical Center, United States
Carlos J. Rosado, Monash University, Australia  

Copyright: © 2018 Gao, Zhou, Liang, Huang, Yang, Chen, Zhang, Yan, Wang, Lu, Wen, Xian and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Shaoxiang Xian, Guangzhou University of Chinese Medicine, The First Affiliated Hospital, No.12 Jichang Road, Baiyun District, Guangzhou, 510405, Guangdong, China, shaoxiangx@hotmail.com
Prof. Lingjun Wang, Guangzhou University of Chinese Medicine, The First Affiliated Hospital, No.12 Jichang Road, Baiyun District, Guangzhou, 510405, Guangdong, China, smu868@hotmail.com