The production of
growth factors by endothelial cells (EC) and other vascular cells may regulate the migration and proliferation of smooth muscle cells in normal and pathological vessel wall processes. We have previously shown that EC production of
platelet-derived growth factor-like
protein (PDGFc) is regulatable, and in particular is inhibited by specific
lipids and by
lipid-containing complexes, e.g. oxidized
low density lipoproteins and
fish oil emulsions. In this report we show that the inhibitory activity of the
fish oils is in turn regulated by a component present in serum. Addition of the
fish oil extract
MaxEPA to bovine aortic EC, in serum-free medium, reduced PDGFc secretion to about 30% that of control cells. Addition of calf serum to the medium almost completely suppressed this inhibitory activity of
MaxEPA, while in contrast,
fetal calf serum augmented the activity. The suppressor activity in calf serum was dose-dependent, with a half-maximal suppression of about 0.1% serum at a
MaxEPA concentration of 50 micrograms/ml. Adult human serum was observed to have a quantitatively similar suppressor activity. The suppressor activity in human serum was identified as
ceruloplasmin since: 1) purified
ceruloplasmin also suppressed the activity of
fish oil, and at concentrations comparable to the inhibitory levels in serum, and 2) removal of
ceruloplasmin from human plasma-derived serum by immunoprecipitation restored the inhibitory activity of
MaxEPA. These results may have implications in the effectiveness of
fish oils as a therapeutic agent for the reduction of intimal thickening in
atherosclerosis.