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Cyclic strain increases protease-activated receptor-1 expression in vascular smooth muscle cellsCyclic strain regulates many vascular smooth muscle cell (VSMC) functions through changing gene expression. This study investigated the effects of cyclic strain on protease-activated receptor-1 (PAR-1) expression in VSMCs and the possible signaling pathways involved, on the basis of the hypothesis that cyclic strain would enhance PAR-1 expression, reflecting increased thrombin activity. Uniaxial cyclic strain (1 Hz, 20%) of cells cultured on elastic membranes induced a 2-fold increase in both PAR-1 mRNA and protein levels. Functional activity of PAR-1, as assessed by cell proliferation in response to thrombin, was also increased by cyclic strain. In addition, treatment of cells with antioxidants or an NADPH oxidase inhibitor blocked strain-induced PAR-1 expression. Preincubation of cells with protein kinase inhibitors (staurosporine or Ro 31-8220) enhanced strain-increased PAR-1 expression, whereas inhibitors of NO synthase, tyrosine kinase, and mitogen-activated protein kinases had no effect. Cyclic strain in the presence of basic fibroblast growth factor induced PAR-1 mRNA levels beyond the effect of cyclic strain alone, whereas no additive effect was observed between cyclic strain and platelet-derived growth factor-AB. Our findings that cyclic strain upregulates PAR-1 mRNA expression but that shear stress downregulates this gene in VSMCs provide an opportunity to elucidate signaling differences by which VSMCs respond to different mechanical forces.
Document ID
20040088639
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Nguyen, K. T.
(Rice University Houston, Texas, United States)
Frye, S. R.
Eskin, S. G.
Patterson, C.
Runge, M. S.
McIntire, L. V.
Date Acquired
August 21, 2013
Publication Date
November 1, 2001
Publication Information
Publication: Hypertension
Volume: 38
Issue: 5
ISSN: 0194-911X
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL-18672
CONTRACT_GRANT: HL-57352
CONTRACT_GRANT: NS-23327
CONTRACT_GRANT: HL-03658
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Cell Biology
Non-NASA Center

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