Platelet-dependent stimulation of prostacyclin synthesis by platelet-derived growth factor

Abstract

Prostacyclin (PGI₂), an unstable metabolite of arachidonic acid synthesized by vascular endothelial and smooth muscle cells, is a potent vasodilator and endogenous inhibitor of platelet aggregation^1–10. Regulation of PGI₂ synthesis by the vessel wall is not well understood^11–16. We have investigated the possibility that a product released from platelet granules during degranulation might modify vessel wall PGI₂ biosynthesis. We report here that a non-dialysable, platelet-dependent factor in serum dramatically stimulates PGI₂ synthesis by cultured bovine aortic endothelium, aortic smooth muscle, and adrenal capillary endothelium. Platelet-derived growth factor (PDGF), a releasable peptide contained within platelet alpha granules^17–20, stimulates PGI₂ synthesis by the above cell types as much as 100-fold. The concentrations of PDGF required to produce these effects are below the level reported in normal human serum¹⁸. We postulate that in vivo released PDGF may increase vessel wall PGI₂ production as part of a negative feedback mechanism controlling platelet aggregation.