Cardiac Fibrosis Alleviated by Exercise Training Is AMPK-Dependent

PLoS One. 2015 Jun 12;10(6):e0129971. doi: 10.1371/journal.pone.0129971. eCollection 2015.

Abstract

Regular exercise can protect the heart against external stimuli, but the mechanism is not well understood. We determined the role of adenosine monophosphate-activated protein kinase (AMPK) in regulating swimming exercise-mediated cardiac protection against β-adrenergic receptor overstimulation with isoproterenol (ISO) in mice. Ten-week-old AMPKα2+/+ and AMPKα2-knockout (AMPKα2-/-) littermates were subjected to 4 weeks of swimming training (50 min daily, 6 days a week) or housed under sedentary conditions. The mice received daily subcutaneous injection of ISO (5 mg/kg/d), a nonselective β-adrenergic receptor agonist, during the last 2 weeks of swimming training. Swimming training alleviated ISO-induced cardiac fibrosis in AMPKα2+/+ mice but not AMPKα2-/- mice. Swimming training activated cardiac AMPK in AMPKα2+/+ mice. Furthermore, swimming training attenuated ISO-induced production of reactive oxygen species (ROS) and expression of NADPH oxidase and promoted the expression of antioxidant enzymes in AMPKα2+/+ mice but not AMPKα2-/- mice. In conclusion, swimming training attenuates ISO-induced cardiac fibrosis by inhibiting the NADPH oxidase-ROS pathway mediated by AMPK activation. Our findings provide a new mechanism for the cardioprotective effects of exercise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Fibrosis
  • Heart Diseases / metabolism*
  • Heart Diseases / pathology
  • Heart Diseases / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / metabolism
  • Myocardium / pathology*
  • NADPH Oxidases / metabolism
  • Physical Exertion*
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • NADPH Oxidases
  • AMP-Activated Protein Kinases

Grants and funding

This work was supported by the Natural Science Foundation of China (NSFC, 81030001); the National Key Basic Research Program of the People’s Republic of China (2012CB51800). YYZ received the fundings. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.