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Record 1 of 50637
Shear stress reduces protease activated receptor-1 expression in human endothelial cells
External Online Source: doi:10.1114/1.1349700
Author and Affiliation:
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.
Abstract: Shear 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.
Publication Date: Feb 01, 2001
Document ID:
20040112500
(Acquired Oct 05, 2004)
Subject Category: LIFE SCIENCES (GENERAL)
Document Type: Journal Article
Publication Information: Annals of biomedical engineering (ISSN 0090-6964); Volume 29; 2; 145-52
Publisher Information: United States
Contract/Grant/Task Num: HL18672; HL57352; NS23327
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: ENDOTHELIUM; GENETICS; METABOLISM; PROTEASE; SHEAR STRESS; BIOENGINEERING; CULTURE MEDIA; CULTURED CELLS; ENZYMES; RIBONUCLEIC ACIDS; STRESSES; THROMBIN
Other Descriptors: ENDOTHELIUM, VASCULAR/DRUG EFFECTS/METABOLISM/SECRETION; RECEPTORS, THROMBIN/GENETICS/METABOLISM; BIOMEDICAL ENGINEERING; CELLS, CULTURED; CULTURE MEDIA, CONDITIONED; DOWN-REGULATION; ENDOTHELIN-1/SECRETION; HUMAN; PROTEIN KINASES/METABOLISM; RNA STABILITY; RNA, MESSENGER/GENETICS/METABOLISM; RECEPTOR, PAR-1; STRESS, MECHANICAL; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, NON-P.H.S; SUPPORT, U.S. GOV'T, P.H.S; THROMBIN/PHARMACOLOGY; NASA DISCIPLINE CELL BIOLOGY; NON-NASA CENTER
Availability Source: Other Sources
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