Modulating the functional contributions of c-Myc to the human endothelial cell cyclic strain response

J Vasc Res. 2010;47(1):80-90. doi: 10.1159/000235928. Epub 2009 Sep 3.


This study addresses whether pathological levels of cyclic strain activate the c-Myc promoter, leading to c-Myc transcription and downstream gene induction in human umbilical vein endothelial cells (HUVEC) or human aortic endothelial cells (HAEC). mRNA and protein expression of c-Myc under physiological (6-10%) and pathological cyclic strain conditions (20%) were studied. Both c-Myc mRNA and protein expression increased 2-3-fold in HUVEC cyclically strained at 20%. c-Myc protein increased 4-fold in HAEC. In HUVEC, expression of mRNA peaked at 1.5-2 h. Subsequently, the effect of modulating c-Myc on potential downstream gene targets was determined. A small molecular weight compound that binds to and stabilizes the silencer element in the c-Myc promoter attenuates cyclic strain-induced c-Myc transcription by about 50%. This compound also modulates c-Myc downstream gene targets that may be instrumental in induction of vascular disease. Cyclic strain-induced gene expression of vascular endothelial growth factor, proliferating cell nuclear antigen and heat shock protein 60 are attenuated by this compound. These results offer a possible mechanism and promising clinical treatment for vascular diseases initiated by increased cyclic strain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Cells, Cultured
  • Chaperonin 60 / metabolism
  • Endothelial Cells / metabolism*
  • Humans
  • Mechanotransduction, Cellular*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / metabolism
  • Stress, Mechanical
  • Time Factors
  • Transcriptional Activation
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism


  • Chaperonin 60
  • MYC protein, human
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A