DOI: 10.1073/pnas.170282597. Molecular mechanism of endothelial growth arrest by laminar shear stress

Molecular mechanism of endothelial growth arrest by laminar shear stress

10.1073/pnas.170282597

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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)/cm 2 or higher, but not at 1.5 dynes/cm 2 . 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.

Bibliography

Lin, K., Hsu, P.-P., Chen, B. P., Yuan, S., Usami, S., Shyy, J. Y.-J., Li, Y.-S., & Chien, S. (2000). Molecular mechanism of endothelial growth arrest by laminar shear stress. Proceedings of the National Academy of Sciences, 97(17), 9385â9389.

Authors 8

Kurt Lin (first)
Pin-Pin Hsu (additional)
Benjamin P. Chen (additional)
Suli Yuan (additional)
Shunichi Usami (additional)
John Y.-J. Shyy (additional)
Yi-Shuan Li (additional)
Shu Chien (additional)

References 32 Referenced 219

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R M Nerem Monogr Atheroscler 15, 117–124 (1990). / Monogr Atheroscler by Nerem R M (1990)
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Y L Hu, S Li, J Y Shyy, S Chien Am J Physiol 277, H1593–H1599 (1999). / Am J Physiol by Hu Y L (1999)
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Q Zhan, S Fan, I Bae, C Guillouf, D A Liebermann, P M O'Connor, A J Fornace Oncogene 9, 3743–3751 (1994). / Oncogene by Zhan Q (1994)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:43 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 2:56 a.m.)
Indexed	1 week, 4 days ago (Aug. 23, 2025, 9:14 p.m.)
Issued	25 years, 1 month ago (Aug. 1, 2000)
Published	25 years, 1 month ago (Aug. 1, 2000)
Published Online	25 years, 1 month ago (Aug. 1, 2000)
Published Print	25 years ago (Aug. 15, 2000)

Funders 0

None

BibTeX

@article{Lin_2000, title={Molecular mechanism of endothelial growth arrest by laminar shear stress}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.170282597}, DOI={10.1073/pnas.170282597}, number={17}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Lin, Kurt and Hsu, Pin-Pin and Chen, Benjamin P. and Yuan, Suli and Usami, Shunichi and Shyy, John Y.-J. and Li, Yi-Shuan and Chien, Shu}, year={2000}, month=aug, pages={9385–9389} }

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  "abstract": "<jats:p>\n            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 \u03bcN)/cm\n            <jats:sup>2</jats:sup>\n            or higher, but not at 1.5 dynes/cm\n            <jats:sup>2</jats:sup>\n            . 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\n            <jats:sup>cip1</jats:sup>\n            , 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\n            <jats:sup>cip1</jats:sup>\n            . 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.\n          </jats:p>",
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