Effects of high intensity training and high volume training on endothelial microparticles and angiogenic growth factors

PLoS One. 2014 Apr 25;9(4):e96024. doi: 10.1371/journal.pone.0096024. eCollection 2014.


Aims: Endothelial microparticles (EMP) are complex vesicular structures shed from activated or apoptotic endothelial cells. As endurance exercise affects the endothelium, the objective of the study was to examine levels of EMP and angiogenic growth factors following different endurance exercise protocols.

Methods: 12 subjects performed 3 different endurance exercise protocols: 1. High volume training (HVT; 130 min at 55% peak power output (PPO); 2. 4 × 4 min at 95% PPO; 3. 4 × 30 sec all-out. EMPs were quantified using flow cytometry after staining platelet-poor-plasma. Events positive for Annexin-V and CD31, and negative for CD42b, were classified as EMPs. Vascular endothelial growth factor (VEGF), migratory inhibiting factor (MIF) and hepatocyte growth factor (HGF) were determined by ELISA technique. For all these measurements venous blood samples were taken pre, 0', 30', 60' and 180' after each intervention. Furthermore, in vitro experiments were performed to explore the effect of collected sera on target endothelial functions and MP uptake capacities.

Results: VEGF and HGF significantly increased after HIT interventions. All three interventions caused a significant decrease in EMP levels post exercise compared to pre values. The sera taken after exercise increased the uptake of EMP in target endothelial cells compared to sera taken under resting conditions, which was shown to be phosphatidylserin-dependent. Increased EMP uptake was associated with an improved protection of target cells against apoptosis. Sera taken prior and after exercise promoted target endothelial cell migration, which was abrogated after inhibition of VEGF.

Conclusion: Physical exercise leads to decreased EMP levels and promotes a phosphatidylserin-dependent uptake of EMP into target endothelial cells, which is associated with a protection of target cells against apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Annexin A1 / physiology
  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Cell-Derived Microparticles / metabolism*
  • Cells, Cultured
  • Coronary Vessels / cytology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology
  • Hepatocyte Growth Factor / blood
  • Humans
  • Intramolecular Oxidoreductases / blood
  • Macrophage Migration-Inhibitory Factors / blood
  • Male
  • Neovascularization, Physiologic
  • Oxygen Consumption
  • Physical Conditioning, Human*
  • Vascular Endothelial Growth Factor A / blood*
  • Young Adult


  • Annexin A1
  • HGF protein, human
  • Macrophage Migration-Inhibitory Factors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Hepatocyte Growth Factor
  • Intramolecular Oxidoreductases
  • MIF protein, human

Grants and funding

This work was supported by the grant funding of the German Sport University Cologne. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.