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

Nicole E. Hurley, Lisa A. Schildmeyer, Kami A. Bosworth, Yumiko Sakurai, Suzanne G. Eskin, Laurence H. Hurley, Larry V. McIntire

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)80-90
Number of pages11
JournalJournal of Vascular Research
Volume47
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • C-Myc
  • Cyclic strain
  • Endothelial cells
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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