Endothelial injury induces vascular smooth muscle cell proliferation in highly localized regions of a direct contact co-culture system

  • Jacot J
  • Wong J
  • 5

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Abstract

Though previous studies have indicated a relationship between the proliferation of endothelial cells and vascular smooth muscle cells (VSMCs) in co-culture, the results have been contradictory and the signaling mechanism poorly understood. In this transmembrane co-culture study, VSMCs and endothelial cells were grown to confluence on opposite sides of a microporous membrane to mimic the intima/media border of vessels. The endothelial layer was injured, and then cultured for 3 days, resulting in partial re-endothelialization. VSMC proliferation across from the injured/partially recovered endothelial region was significantly higher than across from the de-endothelialized region (a sevenfold increase) and the uninjured region (a threefold increase). ELISA indicated that PDGF, which was undetectable in uninjured co-culture and homotypic controls, increased after injury and the addition of a piperazinyl-quinazoline carboxamide PDGF receptor inhibitor blocked VSMC proliferation across from the injured/partially recovered region. We conclude that co-culture signaling initiated by endothelial cell injury locally stimulates VSMC proliferation and that this signaling could be mediated by PDGF-BB.

Author-supplied keywords

  • *Cell Proliferation/drug effects
  • Animals
  • Cattle
  • Cells, Cultured
  • Coculture Techniques/instrumentation/methods
  • Diffusion Chambers, Culture
  • Dose-Response Relationship, Drug
  • Endothelial Cells/cytology/drug effects/*physiolog
  • Enzyme Inhibitors/pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Fatty Acids, Monounsaturated/pharmacology
  • Gap Junctions/drug effects/physiology
  • Graft Occlusion, Vascular/physiopathology
  • Models, Cardiovascular
  • Muscle, Smooth, Vascular/cytology/drug effects/*ph
  • Piperazines/pharmacology
  • Platelet-Derived Growth Factor/physiology
  • Quinazolines/pharmacology
  • Receptors, Vascular Endothelial Growth Factor/anta
  • Structure-Activity Relationship

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Authors

  • J G Jacot

  • J Y Wong

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