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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:801.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Apolipoprotein A-I and A-II Kinetic Parameters as Assessed by Endogenous Labeling With [²H₃]Leucine in Middle-Aged and Elderly Men and Women

Wanda Velez-Carrasco; Alice H. Lichtenstein; Zhengling Li; Gregory G. Dolnikowski; Stefania Lamon-Fava; Francine K. Welty; Ernst J. Schaefer

From the Lipid Metabolism Laboratory (W.V.-C., A.H.L., Z.L., S.L.-F., F.K.W., E.J.S.) and Mass Spectrometry Laboratory (G.G.D.), Jean Mayer USDA Human Nutrition Research Center of Aging at Tufts University, Boston, Mass.

Correspondence to Ernst J. Schaefer, MD, Lipid Metabolism Laboratory, J.M. USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111. E-mail eschaefer{at}hnrc.tufts.edu

Abstract—The purpose of our study was to investigate high density lipoprotein (HDL) apolipoprotein (apo) A-I and apoA-II kinetics in a state of constant feeding after a primed-constant infusion of [5,5,5-²H₃]L-leucine in 32 normolipidemic older men and postmenopausal women (aged 41 to 79 years). ApoA-I and apoA-II were isolated from plasma HDL, and enrichment was determined by gas chromatography/mass spectrometry. The fractional secretion rate was obtained by using a monoexponential equation calculated with the SAAM II program (Department of Bioengineering, University of Washington, Seattle). Mean HDL cholesterol (HDL-C) and total triglyceride levels were 23% higher and 27% lower, respectively, in women than in men. Mean plasma apoA-I levels were 10% greater in women than in men, whereas mean apoA-II levels were similar. HDL size, estimated by gradient-sizing gels and by the HDL-C/apoA-I+apoA-II ratio, was significantly higher in women than in men. Mean apoA-I secretion rates (SRs) were similar in men and women (12.28±3.64 versus 11.96±2.92 mg/kg per day), whereas there was a trend toward a lower (-13%) apoA-I fractional catabolic rate (FCR) in women compared with men (0.199±0.037 versus 0.225±0.062 pools per day, P=0.11). Mean apoA-II SRs (2.21±0.57 versus 2.27±0.91 mg/kg per day) and FCRs (0.179±0.034 versus 0.181±0.068 pools per day) were similar in men and women. For the group as a whole, there was an inverse association between the HDL-C/apoA-I+apoA-II ratio and apoA-I FCR and between the ratio and triglyceride levels. Plasma levels of apoA-I and apoA-II were correlated with their respective SRs but not FCRs. These data suggest a major role for apoA-I and apoA-II SRs in regulating the plasma levels of these proteins, whereas apoA-I FCR might be an important factor contributing to the differences in apoA-I levels between men and postmenopausal women. Moreover, plasma triglyceride levels are important determinants of HDL size and apoA-I catabolism.

Key Words: stable isotopes • apolipoprotein A-I • apolipoprotein A-II • kinetic parameters

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