The potential health benefits of marine oils in vascular disease are being intensively investigated, including their effects on platelets, endothelium, macrophages and lipoproteins (LP). There is also great interest in the appearance of atherogenic LP during post-prandial lipemia, and striking effects of the N-3 fatty acids (FA) in marine lipids on post- prandial lipemia are now well-established. However, no studies have yet defined the post-prandial interactions of LP, endothelium and blood elements in humans or how ingestion of marine oils might alter such processes. The object of the proposed research will be to utilize state- of-the-art GC/MS methods and administration of defined test meals to 10 study platelet/vascular interactions during lipoprotein processing in men and women, and how such effects are changed by the acute and chronic ingestion of marine oils; 20 assess the effects of N-3 FA and alpha- tocopherol on the generation of oxidized LP during post-prandial processing by normal and atherosclerotic subjects, as well as the delivery via the bile of oxygenated lipids to the G.I. tract that could be incorporated into nascent chylomicrons, and 3) investigate the transfer of fatty acids, sterols, their oxygenated derivatives, and alpha-tocopherol to monocytes during post-prandial lipemia following ingestion of marine or control oils, and the effects of marine oils and marine-oil enriched LP on human monocyte and macrophage cholesterol ester metabolism, eicosanoid synthesis and chemotaxis. Physiological and pharmacological approaches will be used to define important aspects of platelet/vascular, vascular/lipoprotein, and lipoprotein/monocyte interactions in humans, compare these events in men and women, and determine how they are influenced by marine oils. By doing so, the proposed project directly addresses in vivo several important hypotheses underlying current theories of human atherogenesis, and thereby will define more clearly the potential health benefits of marine oils in Western societies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL048877-03
Application #
2224970
Study Section
Nutrition Study Section (NTN)
Project Start
1992-08-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Iowa
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Tong, H; Knapp, H R; VanRollins, M (1998) A low temperature flotation method to rapidly isolate lipoproteins from plasma. J Lipid Res 39:1696-704
Knapp, H R (1997) Dietary fatty acids in human thrombosis and hemostasis. Am J Clin Nutr 65:1687S-1698S
VanRollins, M; Kaduce, T L; Fang, X et al. (1996) Arachidonic acid diols produced by cytochrome P-450 monooxygenases are incorporated into phospholipids of vascular endothelial cells. J Biol Chem 271:14001-9
Knapp, H R (1996) n-3 fatty acids and human hypertension. Curr Opin Lipidol 7:30-3
Knapp, H R (1995) Omega-3 fatty acids in respiratory diseases: a review. J Am Coll Nutr 14:18-23
Kopp, U C; Farley, D M; Smith, L A et al. (1995) Essential fatty acid deficiency impairs the responsiveness of renal pelvic sensory receptors. Am J Physiol 268:R164-70
VanRollins, M; Kochanek, P M; Evans, R W et al. (1995) Optimization of epoxyeicosatrienoic acid syntheses to test their effects on cerebral blood flow in vivo. Biochim Biophys Acta 1256:263-74
VanRollins, M (1995) Epoxygenase metabolites of docosahexaenoic and eicosapentaenoic acids inhibit platelet aggregation at concentrations below those affecting thromboxane synthesis. J Pharmacol Exp Ther 274:798-804
VanRollins, M; Knapp, H R (1995) Identification of arachidonate epoxides/diols by capillary chromatography-mass spectrometry. J Lipid Res 36:952-66
Knapp, H R; Hullin, F; Salem Jr, N (1994) Asymmetric incorporation of dietary n-3 fatty acids into membrane aminophospholipids of human erythrocytes. J Lipid Res 35:1283-91

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