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Autophagy mediates the secretion of macrophage migration inhibitory factor from cardiomyocytes upon serum-starvation

Jimin Wu1,2,3,4, Xiangning Deng1,2,3,4, Juan Gao1,2,3,4

  • 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China.

Science China. Life Sciences
|June 19, 2019
PubMed

Insights

Macrophage migration inhibitory factor (MIF) is released from heart cells during ischemia before significant damage occurs. This release is mediated by autophagy, offering potential for early acute coronary syndrome diagnosis.

Area of Science:

  • Cardiology
  • Cell Biology
  • Biochemistry

Background:

  • Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine elevated in acute myocardial infarction.
  • The cellular origin and release mechanism of MIF in cardiac ischemia remain unclear.

Purpose of the Study:

  • To investigate the cellular source and mechanism of MIF release from the heart during ischemic conditions.
  • To explore the potential of MIF as an early diagnostic marker for acute coronary syndrome (ACS).

Main Methods:

  • Neonatal rat cardiomyocytes and fibroblasts were treated with an ischemia-mimic.
  • Plasma samples from patients with acute chest pain were analyzed for MIF levels.
  • Serum-starvation experiments were conducted on rat cardiomyocytes and perfused hearts, with and without autophagy inhibition.

Main Results:

  • Ischemia-mimic treatment induced MIF secretion from cardiomyocytes, not fibroblasts, without significant cell damage.
  • Elevated MIF levels were observed early in ACS patients, preceding cardiac injury markers.
  • Serum-starvation triggered MIF secretion from cardiomyocytes via an autophagy-dependent pathway, suppressed by autophagy inhibition.

Conclusions:

  • Cardiomyocytes are a source of MIF during ischemia, releasing it via an autophagy-dependent mechanism.
  • MIF can be secreted before severe myocardial damage, suggesting its utility in early ACS detection.
  • Understanding MIF secretion pathways may aid in developing novel diagnostic and therapeutic strategies for ACS.
Keywords:
autophagycardiomyocyteischemiamacrophage migration inhibitory factorsecretion

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