Open AccessCardiac Fibrosis Alleviated by Exercise Training Is AMPK-Dependent
Author(s) -
Xiuli Ma,
Yan Fu,
Han Xiao,
Yao Song,
Chen Ruifei,
Jing Shen,
Xiangbo An,
Qiang Shen,
Zijian Li,
Youyi Zhang
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0129971
Subject(s) - ampk , protein kinase a , nadph oxidase , medicine , endocrinology , fibrosis , agonist , amp activated protein kinase , cardiac fibrosis , reactive oxygen species , chemistry , receptor , phosphorylation , oxidative stress , biochemistry
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.