Molecular mechanism of endothelial growth arrest by laminar shear stress

Kurt Lin, Pin Pin Hsu, Benjamin P. Chen, Suli Yuan, Shunichi Usami, John Y J Shyy, Yi Shuan Li, Shu Chien

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

This study was designed to elucidate the mechanism underlying the inhibition of endothelial cell growth by laminar shear stress. Tumor suppressor gene p53 was increased in bovine aortic endothelial cells subjected to 24 h of laminar shear stress at 3 dynes (1 dyne = 10 μN)/cm2 or higher, but not at 1.5 dynes/cm2. One of the mechanisms of the shear-induced increase in p53 is its stabilization after phosphorylation by c-Jun N-terminal kinase. To investigate the consequence of the shear-induced p53 response, we found that prolonged laminar shear stress caused increases of the growth arrest proteins GADD45 (growth arrest and DNA damage inducible protein 45) and p21(cip1), as well as a decrease in phosphorylation of the retinoblastoma gene product. Our results suggest that prolonged laminar shear stress causes a sustained p53 activation, which induces the up-regulation of GADD45 and p21(cip1). The resulting inhibition of cyclin-dependent kinase and hypophosphorylation of retinoblastoma protein lead to endothelial cell cycle arrest. This inhibition of endothelial cell proliferation by laminar shear stress may serve an important homeostatic function by preventing atherogenesis in the straight part of the arterial tree that is constantly subjected to high levels of laminar shearing.

Original languageEnglish (US)
Pages (from-to)9385-9389
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number17
StatePublished - Aug 15 2000

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Endothelial Cells
Growth
DNA Damage
Phosphorylation
Retinoblastoma Genes
Retinoblastoma Protein
Proteins
Cyclin-Dependent Kinases
JNK Mitogen-Activated Protein Kinases
Cell Cycle Checkpoints
Tumor Suppressor Genes
Atherosclerosis
Up-Regulation
Cell Proliferation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Molecular mechanism of endothelial growth arrest by laminar shear stress. / Lin, Kurt; Hsu, Pin Pin; Chen, Benjamin P.; Yuan, Suli; Usami, Shunichi; Shyy, John Y J; Li, Yi Shuan; Chien, Shu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 17, 15.08.2000, p. 9385-9389.

Research output: Contribution to journalArticle

Lin, K, Hsu, PP, Chen, BP, Yuan, S, Usami, S, Shyy, JYJ, Li, YS & Chien, S 2000, 'Molecular mechanism of endothelial growth arrest by laminar shear stress', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 17, pp. 9385-9389.
Lin, Kurt ; Hsu, Pin Pin ; Chen, Benjamin P. ; Yuan, Suli ; Usami, Shunichi ; Shyy, John Y J ; Li, Yi Shuan ; Chien, Shu. / Molecular mechanism of endothelial growth arrest by laminar shear stress. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 17. pp. 9385-9389.
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