Neuregulin‑1: An underlying protective force of cardiac dysfunction in sepsis (Review)

Mol Med Rep. 2020 Jun;21(6):2311-2320. doi: 10.3892/mmr.2020.11034. Epub 2020 Mar 20.

Abstract

Neuregulin-1 (NRG-1) is a type of epidermal growth factor‑like protein primarily distributed in the nervous and cardiovascular systems. When sepsis occurs, the incidence of cardiac dysfunction in myocardial injury is high and the mechanism is complicated. It directly causes myocardial cell damage, whilst also causing damage to the structure and function of myocardial cells, weakening of endothelial function and coronary microcirculation, autonomic dysfunction, and activation of myocardial inhibitory factors. Studies investigating NRG‑1 have been performed using a variety of methods, including in vitro models, and animal and human clinical trials; however, the results are not consistent. NRG‑1/ErbBs signaling is involved in a variety of cardiac processes, from the development of the myocardium and cardiac conduction systems to the promotion of angiogenesis in cardiomyocytes, and in cardio‑protective effects during injury. NRG‑1 may exert a multifaceted cardiovascular protective effect by activating NRG‑1/ErbBs signaling and regulating multiple downstream signaling pathways, thereby improving myocardial cell dysfunction in sepsis, and protecting cardiomyocytes and endothelial cells. It may alleviate myocardial microvascular endothelial injury in sepsis; its anti‑inflammatory effects inhibit the production of myocardial inhibitory factors in sepsis, improve myocardial ischemia, decrease oxidative stress, regulate the disruption to the homeostasis of the autonomic nervous system, improve diastolic function, and offer protective effects at multiple target sites. As the mechanism of action of NRG‑1 intersects with the pathways involved in the pathogenesis of sepsis, it may be applicable as a treatment strategy to numerous pathological processes in sepsis.

Keywords: neuregulin-1; erbB receptors; sepsis; cardiac dysfunction; cardiomyocytes; therapeutic.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiomyopathies / metabolism
  • Endothelial Cells / metabolism
  • Heart Diseases / drug therapy*
  • Heart Diseases / metabolism*
  • Humans
  • Myocardial Ischemia / metabolism
  • Myocardium / metabolism
  • Myocytes, Cardiac / metabolism
  • Neuregulin-1 / genetics
  • Neuregulin-1 / metabolism*
  • Neuregulin-1 / pharmacology*
  • Neuregulin-1 / therapeutic use
  • Oxidative Stress / drug effects
  • Sepsis / complications
  • Sepsis / metabolism*
  • Signal Transduction / drug effects

Substances

  • NRG1 protein, human
  • Neuregulin-1