CHARACTERIZATION OF PROSTACYCLIN SYNTHESIS IN CULTURED HUMAN ARTERIAL SMOOTH-MUSCLE CELLS, VENOUS ENDOTHELIAL-CELLS AND SKIN FIBROBLASTS

The interaction of human platelets with one another and with the blood vessel wall is thought to be regulated in part by a balance between two arachidonic acid metabolites: thromboxane A2, synthesized by platelets, and prostacyclin (PGI2), synthesized by the vessel wall. We have studied the ability of cultured human vascular cells to synthesize PGI2 from arachidonic acid. Four strains of human arterial smooth muscle cells synthesized a mean of 1.36 ng PGI2 per 105 cells, with a range of 0.2-5.3 ng PGI2 per 105 cells among the different strains. Human umbilical vein endothelial cells synthesized a mean of 7.16 ng PGI2 per 105 cells with a range of 2.3-14.0 ng per 105 cells. In contrast, cultured human diploid skin fibroblasts synthesized only 0.27 ng PGI2 per 105 cells with a range of 0.05-0.6 ng per 105 cells. When cultured cells were mixed with platelets, PGI2 synthesis from added arachidonate was reduced rather than stimulated. Thus the major precursor cyclic endoperoxides utilized for PGI2 synthesis are formed within the cells and not from endoperoxides synthesized by platelet cyclooxygenase. Aspirin has been proposed as an anti-thrombotic agent. Aspirin could be ineffective, however, if it inhibited not only platelet cyclooxygenase but that of vessel wall cells as well. Measurement of the rate constant or potency for aspirin inhibition of PGI2 synthesis in cultured cells indicates that the cyclooxygenase in both cell types of the blood vessel wall is 14-44 fold less sensitive to aspirin inactivation than that in platelets, and appropriate levels of aspirin can selectively block human platelet thromboxane A2 synthesis without compromising the capacity of the vasculature to produce PGI2. © 1979.