Development and regression of atherosclerosis in pigs. Effects of n-3 fatty acids, their incorporation into plasma and aortic plaque lipids, and granulocyte function

Abstract

Fifty-one pigs were fed a low-cholesterol basal diet, to which either 10% (by weight) of lard fat (group INORM, n = 7), 2% cholesterol plus 8% lard fat (group II, n = 33), or 2% cholesterol plus 4% lard fat plus 4% fish oil (group IIIPREV, n = 11) was added. In all pigs, the left anterior descending coronary artery and the abdominal aorta were denuded at 1 month. In the first 24 hours thereafter, three animals in group II and two in group IIIPREV died suddenly. After 3 months, 0.5% bile acids was added to the diet in groups II and IIIPREV. After 8 months the degree of atherosclerosis was evaluated in groups INORM and IIIPREV and in 14 animals from group II (IIIND). At 4 months, one animal from Group II died of pneumonia. For the next 4 months (postinduction period), the remaining 15 animals from group II received the basal diet, to which either 10% lard fat (group IILF, n = 6) or 5% lard fat plus 5% fish oil (group IIFO, n = 9) was added. The hypercholesterolemic diet increased plasma cholesterol from 2 to 9-12 mM after 8 months. Fish oil had no major effects on plasma lipids during both induction and postinduction. Superoxide production by granulocytes in response to the membrane receptor-dependent N-formyl-methionyl-leucyl-phenylalanine (fMLP) gave a higher response in group IIIND than in group INORM. In group IIIPREV, the response to phorbol myristate acetate (PMA) and fMLP was lowered, while in groups IIFO and IILF the responses to PMA and fMLP were not affected. The response to serum-treated zymosan was similar in all groups. Abrasion caused increases in free cholesterol (40%) and phospholipids (46%) in the abdominal aortas of group INORM animals. Hypercholesterolemia increased both free and esterified cholesterol in the entire aorta. Fish oil prevented accumulation of free cholesterol in the nonabraded ascending aorta during induction and further accumulation of free cholesterol and phospholipids in the abdominal aorta during postinduction. In the nonabraded ascending aorta, triglycerides were significantly (almost five times) lower in group IIFO than in group IILF. During both induction and postinduction, a large incorporation of n-3 polyunsaturated fatty acids (up to 20%) occurred in plasma and aortic cholesterol esters and phospholipids of groups IIFO and IIIPREV.(ABSTRACT TRUNCATED AT 400 WORDS)