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 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.