Shear stress differentially regulates PGHS-1 and PGHS-2 protein levels in human endothelial cells.
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 PGI2 from arachidonic acid. Endothelial cells were cultured in the presence of 4, 15, or 25 dyn/cm2 shear 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-2 increase depended on the magnitude of the shear stress. The effect of altering shear stress levels on PGHS protein levels in cells preconditioned to either 4, 15, or 25 dyn/cm2 shear stress for 48 h was also studied. Changing shear stress levels effected PGHS-2 but not PGHS-1. Increases in shear stress levels from 4 to 15 or 25 dyn/cm2 caused a decrease in 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/cm2. In summary, the regulation of PGHS-2 by shear stress is dependent upon the magnitude of the shear stress, whereas the regulation of PGHS-1 protein levels seems to be independent of the shear stress magnitude. The regulation of PGHS-1 and PGHS-2 protein levels by shear stress indicates that these proteins play an important role in the maintenance of cardiovascular homeostasis as regulators of PGI2 production.
McCormick
S M
SM
Department of Bioengineering, Rice University, Houston, TX 77251-1892, USA.
Whitson
P A
PA
Wu
K K
KK
McIntire
L V
LV
D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology*; D011464:Epoprostenol / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D018056:Hemorheology; D006706:Homeostasis; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000502:physiology*; D013314:Stress, Mechanical; D013997:Time Factors; D014470:Umbilical Cord / Q000166:cytology
D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases