6-oxo-PGF1 αand 8-epi-PGF2 αin the arterial wall layers of various species: a comparison between intact and atherosclerotic areas

Abstract

PGI2and 8-epi-prostaglandin(PG)F2 αare antagonizing compounds. For both a key role in vascular pathology has been hypothesized. The isoprostane 8-epi-PGF2 αand the stable derivative of PGI2, 6-oxo-PGF1 αwere determined immunologically in the arterial wall of various species including humans. Human arterial tissue contained the highest amounts of 8-epi-PGF2 αand synthesized the lowest PGI2. A significant negative correlation between 8-epi-PGF2 αand 6-oxo-PGF1 αwas observed. Atherosclerotic segments showed significantly higher 8-epi-PGF2αand lower 6-oxo-PGF1 α. 8-epi-PGF2 αin the intima was higher than in the media, the highest amounts being found in foam-cell rich areas. Synthetic (activated) smooth muscle cells were associated with an enhanced 8-epi-PGF2 αas well as 6-oxo-PGF1 α. Tissue samples derived from smokers contained more 8-epi-PGF2 αand produced less PGI2. The by far highest 8-epi-PGF2 α/6-oxo-PGF1 αratio was found in foam cell rich areas. Similar findings were obtained in rabbit and in minipig arteries. The total 8-epi-PGF2 α/6-oxo-PGF1αratio is low in normal tissue, increases significantly in an active atherosclerotic process and seems to be even further increased in an inactive atherosclerotic process. These findings are providing an information on the extent of oxidation injury at various sites of different types of atherosclerotic process.