Exercise Training Has Contrasting Effects in Myocardial Infarction and Pressure Overload Due to Divergent Endothelial Nitric Oxide Synthase Regulation

Elza D. van Deel, Yanti Octavia, Monique C. de Waard, Martine de Boer, Dirk J. Duncker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The beneficial effects of exercise training (EX) on cardiac pathology are well recognized. Previously, we found that the effects of EX on cardiac dysfunction in mice critically depend on the underlying etiology. EX exerted beneficial effects after myocardial infarction (MI); however, cardiac pathology following pressure overload produced by transverse aortic constriction (TAC) was aggravated by EX. In the presented study, we investigated whether the contrasting effects of EX on cardiac dysfunction can be explained by an etiology-specific response of endothelial nitric oxide (NO) synthase (eNOS) to EX, which divergently affects the balance between nitric oxide and superoxide. For this purpose, mice were exposed to eight weeks of voluntary wheel running or sedentary housing (SED), immediately after sham, MI, or TAC surgery. Left ventricular (LV) function was assessed using echocardiography and hemodynamic measurements. EX ameliorated LV dysfunction and remodeling after MI, but not following TAC, in which EX even aggravated fibrosis. Strikingly, EX attenuated superoxide levels after MI, but exacerbated NOS-dependent superoxide levels following TAC. Similarly, elevated eNOS S-glutathionylation and eNOS monomerization, which were observed in both MI and TAC, were corrected by EX in MI, but aggravated by EX after TAC. Additionally, EX reduced antioxidant activity in TAC, while it was maintained following EX in MI. In conclusion, the present study shows that EX mitigates cardiac dysfunction after MI, likely by attenuating eNOS uncoupling-mediated oxidative stress, whereas EX tends to aggravate cardiac dysfunction following TAC, likely due to exacerbating eNOS-mediated oxidative stress.
Original languageEnglish
Article number1968
Number of pages12
JournalInternational journal of molecular sciences
Issue number7
Publication statusPublished - 6 Jul 2018


  • exercise
  • myocardial infarction
  • aortic stenosis
  • oxidative stress
  • nitric oxide synthase
  • ENOS
  • Nitric Oxide Synthase Type III/metabolism
  • Oxidative Stress
  • Ventricular Function, Left
  • Motor Activity
  • Nitric Oxide/metabolism
  • Superoxide Dismutase/metabolism
  • Physical Conditioning, Animal
  • Disease Models, Animal
  • Echocardiography
  • Mice, Inbred C57BL
  • Myocardial Infarction/enzymology
  • Superoxide Dismutase-1/metabolism
  • Animals
  • Aortic Valve Stenosis/enzymology
  • Fibrosis
  • Mice
  • Sedentary Behavior


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