Cultured endothelial cells increase their capacity to synthesize prostacyclin following the formation of a contact inhibited cell monolayer

Abstract

The synthesis of the prostaglandins (PG), prostacyclin (PGI₂), PGE₂, and thromboxane A₂ (TXA₂), has been investigated in actively growing and contact-inhibited bovine aortic endothelial cell cultures. Cells were stimulated to synthesize prostaglandins by exposure to exogenous arachidonic acid or to the endoperoxide PGH₂ and by the liberation of endogenous arachidonic acid from cellular lipids with melittin or ionophore A23187. Increased capacity of the cells to synthesize PGI₂ and PGE₂ was observed as a function of time in culture, regardless of the type of stimulation. TXA₂ production increased with time only upon stimulation of the cells with ionophore A23187. This increased PG synthetic capacity was independent of cell density since it was mainly observed in confluent, nondividing endothelial cell cultures. The fact that increased PGI₂ production in confluent cells was also observed with PGH₂, a direct stimulator of PGI₂ synthetase, implies that this process is independent of the arachidonate concentration within the cells or in the culture medium. This increased capacity is likely to reflect an increased activity of the PG synthetase system associated with the formation of a contact inhibited endothelial cell monolayer. A similar time-dependent increase in the PGI₂ production capacity was also observed during growth of cultured bovine corneal endothelial cells.