Prostacyclin (PGI2)-generation by different types of human atherosclerotic lesions

Unaltered human arterial tissue as well as different types of macroscopically and microscopically characterized atherosclerotic lesions were microdissected under a preparation microscope. The prostacyclin formation was examined using its potent platelet aggregation inhibition in vitro according to Moncada's bioassay. In contrast to different PGI₂-formation in various experimental animal models the generation in the different lesion types in terms of wet weight was statistically significantly (p < 0.001) diminished in comparison to normal control tissue. However, the PGI₂-formation in different lesion types is comparable. Accepting the hypothesis delivered earlier by us, that the arterial wall is able to react upon exogenous noxes with a temporarily enhanced PGI₂-formation, followed (after ceasing) by a decrease of PGI₂-synthesis (exhaustion phenomenon) it can be concluded, that the critical stage is prior to the fatty streak formation, which is a preatherosclerotic lesion. Therefore, PGI₂-generation-exhaustion might be mainly responsible for initiation and progression of atherosclerosis, probably before any detectable morphological alterations.