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Renal denervation restrains the inflammatory response in myocardial ischemia–reperfusion injury

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Abstract

Myocardial ischemia–reperfusion (I/R) injury leads to intensive sympathetic nervous system (SNS) activation and inflammatory reactions. Whether renal sympathetic denervation (RDN) could be a new therapeutic strategy to modulate I/R inflammation and reduce infarct size after myocardial I/R injury needs to be explored. First, we investigated the correlation between plasma norepinephrine concentrations and circulating myeloid cell numbers in patients with acute myocardial infarction. And then, C57BL/6 mice underwent a "two-hit" operation, with 10% phenol applied to bilateral renal nerves to abrogate sympathoexcitation, and a 45-min ligation of the left coronary artery to induce myocardial I/R injury. The effects of RDN on the mobilization of immune cells in mice following myocardial I/R injury were explored. We observed a strong association between SNS overactivation and myeloid cell excessive accumulation in patients. In animal experiments, there was a significant reduction in infarct size per area at risk in the denervated-I/R group when compared to that of the innervated-I/R group (39.2% versus 49.8%; p < 0.005), and RDN also improved the left ventricular ejection fraction by 20% after 1 week. Furthermore, the denervated-I/R group showed a decrease in the number of neutrophils and macrophages in the blood and the myocardium as reflected by immunohistochemical staining and flow cytometry analysis (p < 0.05); the decrease was associated with a significant reduction in the circulating production of IL-1, IL-6 and TNF-α (p < 0.05). In summary, our study reveals a novel link between the SNS activity and inflammatory response undergoing myocardium I/R injury and identifies RDN as a potential therapeutic strategy against myocardium I/R injury via preserving the spleen immune cells mobilization.

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Acknowledgements

This work was supported by the Natural Science Foundation of China (Grant numbers 81470371 and 81870358), the Funds for Jiangsu Provincial Key Medical Discipline (ZDXKB2016013), the Key Projects of Science and Technology of Jiangsu Province (BE2019602) and the Programs of the Science Foundation in Nanjing (ZKX17011).

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Correspondence to Jun Xie or Biao Xu.

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Sun, X., Wei, Z., Li, Y. et al. Renal denervation restrains the inflammatory response in myocardial ischemia–reperfusion injury. Basic Res Cardiol 115, 15 (2020). https://doi.org/10.1007/s00395-020-0776-4

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Keywords

  • Renal denervation
  • Sympathetic nervous system activity
  • Myocardial I/R injury
  • Myocardial inflammation