Period 2-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction

Hum Gene Ther. 2020 Jan;31(1-2):119-128. doi: 10.1089/hum.2019.146.

Abstract

Accumulating evidence indicates that the onset of myocardial infarction (MI) shows obvious circadian rhythmicity. Clinical studies have shown that MIs that occur in the early morning have a poor prognosis, but the mechanisms involved are still unknown. In this study, we showed that the expression level of Period 2 (per2) in the heart of mice is lower in the early morning than at noon and that increasing the expression of per2 in H9C2 cells and rat cardiomyocytes increases autophagy levels. Further studies indicated that overexpression of per2 after an MI improved cardiac function by increasing autophagy. In summary, this study has shown that the circadian clock protein, per2, may be a regulator of MI.

Keywords: AMPK; MI; autophagy; period 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Apoptosis
  • Autophagy / genetics*
  • Disease Models, Animal
  • Echocardiography
  • Gene Expression
  • Heart Function Tests
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Male
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / etiology*
  • Myocardial Infarction / pathology*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Period Circadian Proteins / genetics*
  • Period Circadian Proteins / metabolism
  • Phosphorylation
  • Rats
  • Ventricular Remodeling / genetics*

Substances

  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins
  • Per2 protein, mouse
  • Period Circadian Proteins
  • AMP-Activated Protein Kinases