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Metabolism of apolipoprotein A-II containing triglyceride rich ApoB lipoproteins in humans.

ABSTRACT: To characterize human triglyceride-rich lipoproteins (TRL) with and without apoA-II and to study their metabolism in vivo.Plasma from 11 participants on a controlled diet given a bolus infusion of [D5]l-phenylalanine to label apoB was combined into four pools and applied to anti-apoA-II immunoaffinity columns. Fractions with and without apoA-II were separated into VLDL and IDL by ultracentrifugation; lipids and apolipoproteins were measured. For kinetic measurements, apoB was isolated and hydrolyzed to the constituent amino acids. Tracer enrichment was measured by GCMS. Metabolic rates were determined by SAAM-II.VLDL and IDL with apoA-II comprised 7% and 9% of total VLDL and IDL apoB respectively. VLDL with apoA-II was enriched in apoC-III, apoE, and cholesterol compared to VLDL without apoA-II. Mean apoB FCR of VLDL with apoA-II was significantly lower than for VLDL without apoA-II (2.80 ± 0.96 pools/day v.s. 5.09 ± 1.69 pools/day, P = 0.009). A higher percentage of VLDL with apoA-II was converted to IDL than was cleared from circulation, compared to VLDL without apoA-II (96 ± 8% vs. 45 ± 22%; P = 0.007). The rate constants for conversion of VLDL to IDL were similar for VLDL with and without apoA-II. Thus, a very low rate constant for clearance accounted for the lower FCR of VLDL with apoA-II.VLDL with apoA-II represents a small pool of VLDL particles that has a slow FCR and is predominantly converted to IDL rather than cleared from the circulation.

SUBMITTER: Desai NK

PROVIDER: S-EPMC4509984 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Metabolism of apolipoprotein A-II containing triglyceride rich ApoB lipoproteins in humans.

Desai Nirav K NK Ooi Esther M EM Mitchell Paul D PD Furtado Jeremy J Sacks Frank M FM

Atherosclerosis 20150519 2

<h4>Objective</h4>To characterize human triglyceride-rich lipoproteins (TRL) with and without apoA-II and to study their metabolism in vivo.<h4>Methods</h4>Plasma from 11 participants on a controlled diet given a bolus infusion of [D5]l-phenylalanine to label apoB was combined into four pools and applied to anti-apoA-II immunoaffinity columns. Fractions with and without apoA-II were separated into VLDL and IDL by ultracentrifugation; lipids and apolipoproteins were measured. For kinetic measurem ...[more]

PMID: 26071654

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Project description:BACKGROUND AND OBJECTIVES:Triglyceride-rich lipoproteins may contribute to the high cardiovascular risk of patients with CKD. This study evaluated associations of apo-B and markers of triglyceride-rich lipoproteins with cardiovascular events in people with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Analyses were conducted in 9270 participants with CKD in the Study of Heart and Renal Protection (SHARP): 6245 not on dialysis (mean eGFR 26.5 ml/min per 1.73 m2), and 3025 on dialysis when recruited. Cox regression methods were used to evaluate associations of lipids with incident atherosclerotic and nonatherosclerotic vascular events, adjusting for demographics and clinical characteristics. Hazard ratios (HRs) were calculated per 1 SD higher level for apo-B, HDL cholesterol, LDL cholesterol, triglyceride-rich lipoprotein cholesterol (i.e., total cholesterol minus LDL cholesterol minus HDL cholesterol), non-HDL cholesterol, log triglyceride, and log ratio of triglyceride to HDL cholesterol. RESULTS:During a median follow-up of 4.9 years (interquartile range, 4.0-5.5 years), 1406 participants experienced at least one atherosclerotic vascular event. In multivariable adjusted models, positive associations with atherosclerotic vascular events were observed for apo-B (HR per 1 SD, 1.19; 95% confidence interval, 1.12 to 1.27), triglycerides (1.06; 1.00 to 1.13), the ratio of triglyceride to HDL cholesterol (1.10; 1.03 to 1.18), and triglyceride-rich lipoprotein cholesterol (1.14; 1.05 to 1.25). By contrast, inverse associations with nonatherosclerotic vascular events were observed for each of these lipid markers: apo-B (HR per 1 SD, 0.92; 0.85 to 0.98), triglycerides (0.86; 0.81 to 0.92), the ratio of triglyceride to HDL cholesterol (0.88; 0.82 to 0.94), and triglyceride-rich lipoprotein cholesterol (0.85; 0.77 to 0.94). CONCLUSIONS:Higher apo-B, triglycerides, ratio of triglyceride to HDL cholesterol, and triglyceride-rich lipoprotein cholesterol concentrations were associated with increased risk of atherosclerotic vascular events in CKD. Reducing triglyceride-rich lipoproteins using novel therapeutic agents could potentially lower the risk of atherosclerotic cardiovascular disease risk in the CKD population.

Dataset Information

Metabolism of apolipoprotein A-II containing triglyceride rich ApoB lipoproteins in humans.

Publications

Metabolism of apolipoprotein A-II containing triglyceride rich ApoB lipoproteins in humans.

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