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=l), 2% cholesterol plus 8% lard fat (group II, n=33), or 2% cholesterol plus 4% lard fat plus 4% fish oil (group IIIPREVI n=H) 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 III PRE v 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 I NO RM and IIIPREV and in 14 animals from group II (HIND)-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 11,^, n=6) or 5% lard fat plus 5% fish oil (group II ro , 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 A'-forniyl-methionyl-leucyl-phenylalanine (fMLP) gave a higher response in group II IND than in group INORM-In group IIIPREV > the response to phorbol myristate acetate (PMA) and fMLP was lowered, while in groups II TO and 11,^ 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 II F0 than in group II,j.. 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 II ro and IIIPREV In plasma lipids the major fatty acid was always 20: Sn-3, but in aortic lipids the incorporation of its elongated product 22: 5n-3 was generally equal to 20: 5n-3. Sudanophilia of the aorta was 0% for group I NO RM > 33% for group II )ND , 35% for group HI PREV , 9% for group IIu, and 7% for group II FO . Luminal encroachment of the coronary arteries in groups I NO RM and II IND was similar. Fish oil (group IIIPREV) had no effect on the development of coronary atherosclerosis. Despite the normocholesterolemia during the postinduction period in group II LF , coronary atherosclerosis progressed to 12% in the right coronary artery and to 18% in the left anterior descending coronary artery, while in group II F0 these values were 5% and 10%, respect...

Does Therapeutic Intervention Achieve Slowing of Progression or Bona Fide Regression of Atherosclerotic Lesions?

“…24 The induction of atherosclerosis for 8 months, followed by a regression period of 4 months that included feeding of fish oil, did not induce the regression of atherosclerosis but prevented the progression of established lesions. 25 In a later study, 26 the effect of fish oil was examined in minipigs fed the atherogenic diet for 8 months followed by a normal diet alone or with fish oil. Although significant regression of lesions in the aorta and in carotid arteries occurred in animals on the regression diet, there was no potentiation of regression by the addition of fish oil.…”

“…Nine patients in the apheresis group and 11 in the medication group were classified as progressors, and 2 and 5 patients, respectively, were classified as regressors. In a prospective study, 61 25 FH heterozygotes were treated with LDL apheresis and drugs and 11 patients were treated with drugs only; the patients underwent QCA 2.5 years thereafter. The frequency of regression or no progression was significantly higher in the apheresis group.…”

Fish oil and the prevention and regression of atherosclerosis

“…Animal studies with hypercholesterolemia Tables 2-4 list the in vivo studies in rabbits [58][59][60][61][62][63][64][65][66][67][68][69], swine [23,28,[70][71][72][73] and monkeys [74][75][76], respectively, on the effects of fish oil on the prevention of atherosclerosis and provides details such as the dietary regimen, duration of study, etc. Except in the Watanabe hereditary hyperlipidemic rabbit and one study in pigs [73], all atherogenic diets are highcholesterol diets, and in case of the swine model [28,[70][71][72], bile acids were also needed to enhance hypercholesterolemia.…”

“…Except in the Watanabe hereditary hyperlipidemic rabbit and one study in pigs [73], all atherogenic diets are highcholesterol diets, and in case of the swine model [28,[70][71][72], bile acids were also needed to enhance hypercholesterolemia. In small animals (rabbits) usually only the aorta has been used to evaluate the anti-atherogenic effect of fish oil.…”

“…The differences in the bodyweights of rabbits and the type of oil (organic extracts or transethylesterified lipids) with different n-3 fatty acid content invalidate any comparison within this species. The degree of incorporation of 20:5n-3 and 22: 6n-3 into plasma phospholipids might be an indication for an effective dose, but to date only one study [28] reports on the fatty acid distribution of plasma phospholipids after fish oil feeding. The most consistent element throughout the studies in rabbits, pigs and monkeys appears to be the way atherosclerosis is measured in their vessels.…”