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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1703.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Interrelationships Between Human Apolipoprotein A-I and Apolipoproteins B-48 and B-100 Kinetics Using Stable Isotopes

Francine K. Welty; Alice H. Lichtenstein; P. Hugh R. Barrett; Gregory G. Dolnikowski; Ernst J. Schaefer

From the Lipid Metabolism Laboratory (F.K.W., A.H.L., G.G.D., E.J.S.), Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass; the Division of Cardiology (F.K.W.), Beth Israel Deaconess Medical Center, and the School of Medicine and Pharmacology (P.H.R.B.), University of Western Australia, Perth, Australia.

Correspondence to Francine K. Welty, Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center at Tufts University, 711 Washington St, Boston, MA 02111. E-mail fwelty{at}bidmc.harvard.edu

Objective— Our purpose was to determine the relationship between apolipoprotein (apo) A-I and apoB-48 and apoB-100 metabolism in moderately hypercholesterolemic humans.

Methods and Results— The kinetics of apoA-I within high-density lipoprotein (HDL), apoB-48 and apoB-100 within triglyceride-rich lipoproteins, and apoB-100 within intermediate-density lipoprotein and low density-lipoprotein (LDL) were examined with a primed constant infusion of [5,5,5-²H₃] leucine in the fed state (hourly feeding) in 23 subjects after consumption of a 36% total fat diet. Lipoproteins were isolated by ultracentrifugation; apolipoproteins by SDS-PAGE gels; and isotope enrichment assessed by gas chromatograph/mass spectrometry. Kinetic parameters were calculated by multicompartmental modeling of the data with SAAM II. ApoA-I production rate (PR) was correlated with LDL apoB-100 pool size (PS; r=0.49; P=0.017) and LDL cholesterol (r=0.61; P=0.002), whereas apoA-I fractional catabolic rate (FCR) was inversely correlated with apoB-48 FCR (r=–0.40; P=0.05) but not with very low-density lipoprotein apoB-100 FCR.

Conclusions— Two links exist between apoA-I and apoB kinetics: 1) when LDL apoB-100 PS is high, there is increased apoA-I PR; and 2) delayed chylomicron remnant clearance (represented by apoB-48 FCR) is associated with enhanced apoA-I FCR, a finding indicating that alterations in intestinal lipoproteins may be more important in determining HDL cholesterol levels than changes in liver lipoproteins.

Using stable isotopes in humans, 2 links were observed between apoA-I and apoB kinetics: (1) when LDL apoB-100 PS is high, there is increased apoA-I PR; and (2) delayed chylomicron remnant clearance is associated with enhanced apoA-I FCR, indicating that alterations in intestinal lipoproteins may be more important in determining HDL-C levels than changes in liver lipoprotein particles.

Key Words: apolipoprotein A-I • apolipoprotein B • lipoprotein metabolism • stable isotopes • HDL cholesterol

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