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Renalase improves pressure overload-induced heart failure in rats by regulating extracellular signal-regulated protein kinase 1/2 signaling

Abstract

Renalase, a novel flavoprotein that is mainly expressed in the kidney and heart, plays a crucial role in hypertension. Recent studies have shown that renalase is expressed at low levels in the serum of patients with heart failure, while the role of renalase and its mechanism in cardiac failure is unclear. Adult Sprague-Dawley (SD) rats were used to investigate the role and function of renalase in the pathological process of transverse aortic constriction (TAC)-induced heart failure. Renalase-human protein chip analysis showed that renalase was directly associated with P38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling. We further used lentivirus-mediated RNA interference to study the role of renalase in the progression of pathological ventricular hypertrophy and found that renalase inhibition attenuated the noradrenaline-induced hypertrophic response in vitro or the pressure overload-induced hypertrophic response in vivo. Recombinant renalase protein significantly alleviated pressure overload-induced cardiac failure and was associated with P38 and ERK1/2 signaling. These findings demonstrate that renalase is a potential biomarker of hypertrophy and that exogenous recombinant renalase is a potential and novel drug for heart failure.

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Acknowledgements

The study was supported by the National Natural Science Foundation of China (NSFC) Projects (Nos. 81800271 and 81670335) and the Natural Science Foundation of Hunan Province (No. 2019JJ50920).

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XL and WJ provided the general outline of the manuscript and designed the research study, XL and YW performed all experiments and wrote the manuscript, and CQ and YY verified and analyzed the raw data after the experiments. ZL provided assistance with our animal experiments.

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Correspondence to Xiaogang Li.

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Wu, Y., Quan, C., Yang, Y. et al. Renalase improves pressure overload-induced heart failure in rats by regulating extracellular signal-regulated protein kinase 1/2 signaling. Hypertens Res 44, 481–488 (2021). https://doi.org/10.1038/s41440-020-00599-6

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Keywords

  • Renalase
  • Cardiac hypertrophy
  • Cardiac failure
  • ERK 1/2

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