[Anti-thrombotic and anti-atherogenic action of eicosapentaenoic acid].
Epidemiological studies performed in Greenland Eskimos and Japanese indicated that ingestion of fish meat rich in omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), reduces the incidence of cerebro- and cardiovascular thrombotic diseases. Therefore, the effect of administration of purified EPA, derived from sardine oil, on hemorrheological properties and serum lipids in patients with thrombotic disorders was studied. Dietary supplementation of EPA resulted in decrease in platelet aggregability with reduction of TXA2 production, prolongation of bleeding time, decrease of platelet adhesiveness, increase of red cell deformability, and improvement of serum lipid concentration. Decrease in platelet TXA2 production may be ascribed to the decrease in arachidonate (AA) content of platelet membrane, inhibition of AA release from platelet membrane and competitive inhibition of AA metabolism at the level of cyclo-oxygenase, by EPA. Administration of EPA increased PGI2 production in the rat thoracic aorta and co-culture of rat aorta smooth muscle cell with EPA also increased PGI2 production, but suppressed smooth muscle cell proliferation. This may be explained by a EPA-derived peroxide stimulation of cyclo-oxygenase activity. Administration of EPA decreased platelet-derived growth factor (PDGF) production in rat peritoneal macrophages. In EPA-rich peritoneal macrophages from rat given EPA, incorporation of acetyl LDL and accumulation of cholesterol in macrophages decreased. This may indicate that dietary supplementation of EPA suppress foam cell formation. An interesting finding is that EPA-rich LDL obtained from rabbits given EPA is less susceptible to Cu(2+)-catalyzed oxidative modification. This seems to indicate that EPA may also suppress lipid peroxidation of lipoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)
Tamura
Y
Y
2nd Dept. of Int. Med. Chiba Univ. Med. School.
Hirai
A
A
Terano
T
T
Saitoh
H
H
D016718:Arachidonic Acid / Q000378:metabolism; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000517:prevention & control; D015118:Eicosapentaenoic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D011464:Epoprostenol / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control; D013928:Thromboxane A2 / Q000378:metabolism
D005343:Fibrinolytic Agents; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013928:Thromboxane A2; D015118:Eicosapentaenoic Acid; D011464:Epoprostenol