The effect of shear stress on the uptake and metabolism of arachidonic acid by human endothelial cells

Abstract

The uptake and metabolism of arachidonic acid (AA) by human umbilical vein endothelial cells was studied for cells in stationary culture and for cells exposed to physiological levels of shear stress. For cells grown in stationary culture, the initial incorporation of arachidonic acid was primarily into diacylglycerol and phospholipids. Cells exposed to flow incorporated labeled arachidonic acid at a similar rate as cells maintained in stationary culture; however, the distribution of the label was altered by flow. The incorporation of arachidonic acid into diacylglycerol and phosphatidylinositol was increased in cells exposed to flow. The largest increase occurred for cells exposed to arterial levels of shear stress for the shortest time period studied, 0.5 h. Prostacyclin (PGI2) and PGF2 alpha were the principal arachidonic acid metabolites formed. Shear stress-stimulated cells preferentially produced PGI2 relative to other eicosanoid products. The initiation of flow caused a burst of AA metabolism which was highly specific for PGI2. This might represent an increase in the turnover of phosphatidylinositol-bound arachidonic acid which is specifically converted to PGI2 as a result of flow-induced membrane stresses.