PROGRAM PROJECT FATTY ACIDS, LIPOPROTEINS &LIPID OXIDAT

  • Knapp, Howard (PI)
  • Field, F. Jeffrey (PI)
  • Chappell, David (PI)
  • Spector, Arthur (PI)
  • Weintraub, Neal Lee (PI)

Project: Research project

Description

The objective of this Program Project is to provide new insight into the
relationship between fatty acids and cardiovascular disease, with emphasis
on mechanisms involved in hyperlipidemia and atherosclerosis. Our goals
are to determine how polyunsaturated fatty acids (PUFA) affect lipoprotein
production and removal mechanisms, how postprandial lipoproteins enriched
in omega-3 PUFA influence vascular prostanoid formation, and how tissue
PUFA content and composition relates to lipid peroxidation and oxidized
lipoproteins. The Program consists of four research projects and two core
units. Project 1 (Spector) deals with the role of PUFA in cell function,
with emphasis on lipid peroxidation and the detection of lipid radicals in
intact cells. Project 2 (Field) concerns the role of fatty acids in
intestinal lipoprotein formation, including the relationship between
intestinal lipoprotein formation, including the relationship between
intestinal processing of cholesterol and the regulation of apolipoprotein
B formation. Project 3 (Chappell) will characterize the properties of
postprandial lipoproteins formed in response to acute and chronic omega-6
PUFA ingestion, as well as the effect of enrichment with these PUFA on
lipoprotein binding to receptors and catabolism. Project 4 (Knapp) deals
with the effects of ingestion of marine oils, the role of postprandial
lipoproteins containing omega-3 PUFA on eicosanoid production at the
vascular interface, and the effect of fatty acid oxidation products in the
bile on chylomicron formation. These projects are supported by a Cell
Culture Core (Spector) and an Administrative Core (Spector). Among the
novel features of this program is the interplay between human investigation
and the use of cell culture models, the application of electron
paramagnetic resonance and spin traps to detect lipid radicals in intact
cells, and the development of mass spectrometry methods to measure
eicosanoid formation and oxidized lipid products in clinical studies. The
findings will increase our understanding of the mechanisms through which
PUFA exert their protective effects against cardiovascular diseases.
StatusFinished
Effective start/end date9/30/928/31/03

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Coronary Circulation
Blood Vessels
Coronary Vessels
Microvessels
Acids
Endothelial Cells
Endothelium
Swine
Lipids
Endothelium-Dependent Relaxing Factors
Bradykinin
Microcirculation
Arachidonic Acid
Vasodilation
Cytochrome P-450 Enzyme System
Phospholipids
Hydrolysis
Central Nervous System

ASJC

  • Medicine(all)