Apolipoprotein A-I and A-II kinetic parameters as assessed by endogenous labeling with [H-2(3)] leucine in middle-aged and elderly men and women

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 feedin g after a primed-constant infusion of [5,5,5-H-2(3)](L)-leucine in 32 normo lipidemic 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 ob tained by using a monoexponential equation calculated with the SAAM II prog ram (Department of Bioengineering, University of Washington, Seattle). Mean HDL cholesterol (HDLC) and total triglyceride levels were 23% higher and 2 7% lower, respectively, in women than in men. Mean plasma apoA-I levels wer e 10% greater in women than in men, whereas mean apoA-II levels were simila r. HDL size, estimated by gradient-sizing gels and by the HDLC/apoA-I+apoA- II ratio, was significantly higher in women than in men. Mean apoA-I secret ion 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 an d apoA-I FCR and between the ratio and triglyceride levels. Plasma levels o f 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 importa nt factor contributing to the differences in apoA-I levels between men and postmenopausal women. Moreover, plasma triglyceride levels are important de terminants of HDL size and apoA-I catabolism.