Fish oil rich in omega-3 fatty acids added to a butter (BT) containing diet that is highly atherogenic for swine results in modestly lower plasma cholesterol (CH) levels (approximately 20%), marked shifts in distributions of lipoproteins (LP) from predominantly those with B and E apoproteins to predominantly those with only B, and in profoundly smaller atherosclerotic lesions with fewer cells and less necrosis. We have several hypotheses in relation to these observations: (1) the reduced lesion size is due mainly to the shift from larger apo B, E LP to the smaller apo B LP; (2) the apo B LP as compared to apo, B,E LP are in relation to the intimal cells: (a) taken up less readily especially in B, E receptor down regulated state (b) less active in promoting cell proliferation, (c) less cytotoxic; (3) effect of omega-3 rich fish oil on altering plasma LP distributions and reducing atherosclerosis development is far greater than that of omega-6 rich vegetable oils; (4) TBARS levels in the plasma which are elevated with fish oil are not reflecting increased necrosis or other activity in the lesions. The proposed in vivo and in vitro studies wth swine are designed to obtain information that should be helpful in evaluating the above hypothesis. The in vivo studies involve feeding swine BT and BT + FO atherogenic diets alon with several other diets used for comparative purposes. Plasma LP fractions will be compared with emphasis on those containing apo B, E versus those containing only apo B. We shall also compare atherosclerosis development in several anatomic sites with attention to lesion sizes, cell numbers and types, extent of necrosis and (3H)TdR labeling indices. In the vitro studies we shall investigate and compare the effects of specific lipoprotein fractions on: (1) cell proliferation, (2) cell death and (3) uptake of lipid.
| Schmee, J; Kim, D N; Ross, J S et al. (1993) Exponential relationship between plasma cholesterol levels and atherosclerotic lesion size in hyperlipidemic swine. Exp Mol Pathol 59:177-85 |
| Kim, D N; Schmee, J; Baker, J E et al. (1993) Dietary fish oil reduces microthrombi over atherosclerotic lesions in hyperlipidemic swine even in the absence of plasma cholesterol reduction. Exp Mol Pathol 59:122-35 |
| Kim, D N; Schmee, J; Lee, C S et al. (1991) Comparison of effects of fish oil and corn oil supplements on hyperlipidemic diet induced atherogenesis in swine. Atherosclerosis 89:191-201 |
| Kim, D N; Ho, H T; Lawrence, D A et al. (1989) Modification of lipoprotein patterns and retardation of atherogenesis by a fish oil supplement to a hyperlipidemic diet for swine. Atherosclerosis 76:35-54 |
