Sheer stress differentially regulates PGHS-1 and PGHS-2 protein levels in human endothelial cells

The secretion of prostacyclin (PGI(2)) by endothelial cells is regulated by shear stress. Prostaglandin H synthase (PGHS) is considered to be a key Li miting enzyme in the synthesis of PGI, from arachidonic acid. Endothelial c ells were cultured in the presence of 4, 15, or 25 dyn/cm(2) shear stress u sing 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 /cm(2) shear stress PGHS-1 and PGHS-2 protein levels initially decreased. T he decrease was followed by a sustained increase for PGHS-1 but only a tran sient 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 leve ls on PGHS protein levels in cells preconditioned to either 4, 15, or 25 dy n/cm(2) shear stress for 48 h was also studied. Changing shear stress level s effected PGHS-2 but not PGHS-1. Increases in shear stress levels from 4 t o 15 or 25 dyn/cm(2) caused a decrease in PGHS-1. 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/cm(2). In summary, the regulation of PGHS-2 b y sheer stress is dependent upon the magnitude of the shear stress, whereas the regulation of PGHS-1 protein levels seems to be independent of the she ar 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 ma intenance of cardiovascular homeostasis as regulators of PGI(2) production. (C) 2000 Biomedical Engineering Society. [S0090-6964(00)00707-4].