Serum factor that blocks the action of fish oils on endothelial cell production of platelet-derived growth factor is ceruloplasmin.
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.
Fox
P L
PL
Department of Vascular Cell Biology, Cleveland Clinic Research Institute, Ohio.
Salvatore
M F
MF
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005395:Fish Oils / Q000494:pharmacology*; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D001798:Blood Proteins; D005395:Fish Oils; D010982:Platelet-Derived Growth Factor; D002570:Ceruloplasmin