Frontiers in Physiology (Sep 2018)

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

  • Wenbin Gao,
  • Wenbin Gao,
  • Wenbin Gao,
  • Zheng Zhou,
  • Zheng Zhou,
  • Zheng Zhou,
  • Birong Liang,
  • Birong Liang,
  • Birong Liang,
  • Yusheng Huang,
  • Yusheng Huang,
  • Yusheng Huang,
  • Zhongqi Yang,
  • Zhongqi Yang,
  • Zhongqi Yang,
  • Yang Chen,
  • Yang Chen,
  • Lu Zhang,
  • Lu Zhang,
  • Lu Zhang,
  • Cui Yan,
  • Cui Yan,
  • Cui Yan,
  • Jiajia Wang,
  • Jiajia Wang,
  • Jiajia Wang,
  • Lu Lu,
  • Lu Lu,
  • Lu Lu,
  • Zhaorui Wen,
  • Zhaorui Wen,
  • Shaoxiang Xian,
  • Shaoxiang Xian,
  • Shaoxiang Xian,
  • Lingjun Wang,
  • Lingjun Wang,
  • Lingjun Wang

DOI
https://doi.org/10.3389/fphys.2018.01333
Journal volume & issue
Vol. 9

Abstract

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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.

Keywords