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Shear Stress Differentially Regulates PGHS-1 and PGHS-2 Protein Levels in Human Endothelial Cells

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Abstract

The secretion of prostacyclin (PGI2) by endothelial cells is regulated by shear stress.Prostaglandin H synthase (PGHS) is considered to be a key limiting enzyme in the synthesis of PGI2from arachidonic acid. Endothelial cells were cultured in the presence of 4, 15, or 25 dyn/cm2shear stress using a parallel plate flow chamber to assess the effect of shear stress on both PGHS isoforms, PGHS-1 and PGHS-2.In cells exposed to 4, 15, or 25 dyn/cm2 shear stress PGHS-1 and PGHS-2 protein levels initially decreased.The decrease was followed by a sustained increase for PGHS-1 but only a transient increase for PGHS-2. The duration of the PGHS-2increase depended on the magnitude of the shear stress. The effect of altering shear stress levels on PGHS protein levels in cellspreconditioned to either 4, 15, or 25 dyn/cm2 shear stress for 48 h was also studied. Changing shear stresslevels effected PGHS-2 but not PGHS-1. Increases in shear stress levels from 4 to 15 or 25 dyn/cm2 caused a decreasein PGHS-2. In contrast, decreases in shear stress levels from 15 or 25 to 4 dyn/cm2 caused PGHS-2 to increase.There was a continual decrease in PGHS-2 when the shear stress was changed from 15 to 25 or 25 to 15 dyn/cm2In summary, the regulation of PGHS-2 by shear stress is dependent upon the magnitude of the shear stress, whereas the regulation of PGHS-1protein levels seems to be independent of the shear stress magnitude. The regulation of PGHS-1 and PGHS-2 protein levels by shear stressindicates that these proteins play an important role in the maintenance of cardiovascular homeostasis as regulators of PGI2production. © 2000 Biomedical Engineering Society.

PAC00: 8717-d, 8719Rr

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Authors and Affiliations

  1. Department of Bioengineering, Rice University, Houston, TX

    Susan M. McCormick & Larry V. McIntire

  2. Astronaut Office, National Aeronautics and Space Administration, Lyndon B. Johnson Space Center, Houston, TX

    Peggy A. Whitson

  3. Department of Internal Medicine, Division of Hematology and Vascular Biology Research Center, University of Texas-Houston, Houston, TX

    Kenneth K. Wu

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  1. Susan M. McCormick
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  2. Peggy A. Whitson
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  3. Kenneth K. Wu
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  4. Larry V. McIntire
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McCormick, S.M., Whitson, P.A., Wu, K.K. et al. Shear Stress Differentially Regulates PGHS-1 and PGHS-2 Protein Levels in Human Endothelial Cells. Annals of Biomedical Engineering 28, 824–833 (2000). https://doi.org/10.1114/1.1289472

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