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Shear stress reduces protease activated receptor-1 expression in human endothelial cellsShear stress has been shown to regulate several genes involved in the thrombotic and proliferative functions of endothelial cells. Thrombin receptor (protease-activated receptor-1: PAR-1) increases at sites of vascular injury, which suggests an important role for PAR-1 in vascular diseases. However, the effect of shear stress on PAR-1 expression has not been previously studied. This work investigates effects of shear stress on PAR-1 gene expression in both human umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells (HMECs). Cells were exposed to different shear stresses using a parallel plate flow system. Northern blot and flow cytometry analysis showed that shear stress down-regulated PAR-1 messenger RNA (mRNA) and protein levels in both HUVECs and HMECs but with different thresholds. Furthermore, shear-reduced PAR-1 mRNA was due to a decrease of transcription rate, not increased mRNA degradation. Postshear stress release of endothelin-1 in response to thrombin was reduced in HUVECs and HMECs. Moreover, inhibitors of potential signaling pathways applied during shear stress indicated mediation of the shear-decreased PAR-1 expression by protein kinases. In conclusion, shear stress exposure reduces PAR-1 gene expression in HMECs and HUVECs through a mechanism dependent in part on protein kinases, leading to altered endothelial cell functional responses to thrombin.
Document ID
20040112500
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Nguyen, K. T.
(Institute of Biosciences and Bioengineering, Rice University Houston, TX, United States)
Eskin, S. G.
Patterson, C.
Runge, M. S.
McIntire, L. V.
Date Acquired
August 21, 2013
Publication Date
February 1, 2001
Publication Information
Publication: Annals of biomedical engineering
Volume: 29
Issue: 2
ISSN: 0090-6964
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL18672
CONTRACT_GRANT: HL57352
CONTRACT_GRANT: NS23327
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Cell Biology

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