Cyclic strain regulates pro-inflammatory protein expression in porcine aortic valve endothelial cells

J Heart Valve Dis. 2008 Sep;17(5):571-7; discussion 578.


Background and aim of the study: The endothelium of diseased heart valves is known to express the adhesion molecules VCAM-1, ICAM-1 and E-selectin, while healthy valves lack these pro-inflammatory proteins. The study aim was to determine if mechanical forces were responsible for the pro-inflammatory reaction in aortic valve endothelial cells.

Methods: Isolated porcine aortic valve endothelial cells (PAVEC) were cultured and seeded onto BioFlexTM culture plates. The cells were exposed to equibiaxial cyclic strains of 5, 10 and 20% for 24 h in a Flexcell FX-4000T Tension Plus system at 1 Hz. Pro-inflammatory protein expression was detected through the use of monoclonal antibodies via fluorescence-assisted cell sorting (FACS) and confocal laser scanning microscopy (CLSM).

Results: Pro-inflammatory protein expression was evident at cyclic strains of 5 and 20%, while a 10% strain did not elicit an inflammatory response. Confocal images indicated a disrupted endothelial monolayer, evidence of significant cell death, and the presence of all adhesion molecules at 5% strain. PAVEC exposed to 10% cyclic strain failed to express any of the pro-inflammatory proteins, while the cellular monolayer appeared near-confluent and characteristically similar to cellular images captured prior to cyclic stretching. CLSM images of PAVEC cyclically stretched by 20% demonstrated a similar proinflammatory reaction to those with 5% strain, while the cellular environment also showed decreased monolayer integrity. FACS data showed a significant up-regulation of the membrane-bound VCAM-1-, ICAM-1- and E-selectin-positive cells at 5% and 20% strain, compared to 10% strain and controls.

Conclusion: The finding that equibiaxial cyclic strain regulates the pro-inflammatory response in PAVEC suggests that alterations in the mechanical environment of heart valves may contribute to valve pathogenesis.

MeSH terms

  • Animals
  • Aortic Valve / physiopathology*
  • Biomechanical Phenomena
  • Cell Death / physiology
  • E-Selectin / metabolism*
  • Endothelial Cells / physiology*
  • Female
  • Flow Cytometry
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Microscopy, Confocal
  • Stress, Physiological / physiology
  • Swine
  • Up-Regulation / physiology
  • Vacuum
  • Vascular Cell Adhesion Molecule-1 / metabolism*


  • E-Selectin
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1