Metabolism of high density lipoprotein subfractions

Colvin, Perry L.; Parks, John S.

doi:10.1097/00041433-199908000-00004

Cited by 42 publications

(26 citation statements)

References 27 publications

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“…The remodeling of pre␤ LpA-I to medium HDLs does not require LCAT or ABCA1 but may be enhanced by these proteins. Finally, in hA-I Tg mice as well as in previous studies of nonhuman primates (25,26,47), there was no evi- Fig. 7.…”

Section: Discussionsupporting

confidence: 64%

Preβ high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice

Lee

Lanningham-Foster

Boudyguina

et al. 2004

Journal of Lipid Research

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We compared the in vivo metabolism of pre ␤ HDL particles isolated by anti-human apolipoprotein A-I (apoA-I) immunoaffinity chromatography (LpA-I) in human apoA-I transgenic (hA-I Tg) mice with that of lipid-free apoA-I (LFA-I) and small LpA-I. After injection, pre ␤ LpA-I were removed from plasma more rapidly than were LFA-I and small LpA-I. Pre ␤ LpA-I and LFA-I were preferentially degraded by kidney compared with liver; small LpA-I were preferentially degraded by the liver. Five minutes after tracer injection, 99% of LFA-I in plasma was found to be associated with medium-sized (8.6 nm) HDL, whereas only 37% of pre ␤ tracer remodeled to medium-sized HDL. Injection of pre ␤ LpA-I doses into C57Bl/6 recipients resulted in a slower plasma decay compared with hA-I Tg recipients and a greater proportion ( Ͼ 60%) of the pre ␤ radiolabel that was associated with medium-sized HDL. Pre ␤ LpA-I contained one to four molecules of phosphatidylcholine per molecule of apoA-I, whereas LFA-I contained less than one. We conclude that pre ␤ LpA-I has two metabolic fates in vivo, rapid removal from plasma and catabolism by kidney or remodeling to medium-sized HDL, which we hypothesize is determined by the amount of lipid associated with the pre ␤ particle and the particle's ability to bind to medium-sized HDL.

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Section: Discussionsupporting

confidence: 64%

Preβ high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice

Lee

Lanningham-Foster

Boudyguina

et al. 2004

Journal of Lipid Research

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“…Given the propensity for SR-BI-generated HDL remnants to rapidly remodel to form larger particles, it seems unlikely that small remnants ever accumulate to detectable levels in normal HDL metabolism. In kinetic studies in nonhuman primates using HDL particles isolated by immunoaffinity and gel filtration, Colvin and Parks noted that apoA-I on large HDL particles cleared from the plasma without appearing on smaller HDL subfractions (29,30). Although this suggests that apoA-I on large HDL particles is not recycled through small HDL intermediates, our data shows that apoA-I can indeed rapidly cycle between particles of different sizes.…”

Section: Figmentioning

confidence: 47%

The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake

Webb

Cai

Ziemba

et al. 2002

Journal of Lipid Research

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Scavenger receptor class B type I (SR-BI) delivers cholesterol ester from HDL to cells via a selective uptake mechanism, whereby lipid is transferred from the core of the particle without concomitant degradation of the protein moiety. The precise metabolic fate of HDL particles after selective lipid uptake is not known. To characterize SR-BImediated HDL processing in vivo, we expressed high levels of this receptor in livers of apoA-I Ϫ / Ϫ mice by adenoviral vector gene transfer, and then injected the mice with a bolus of human HDL 2 traced with 125 I-dilactitol tyramine. HDL recovered from apoA-I Ϫ / Ϫ mice over-expressing SR-BI was significantly smaller than HDL recovered from control mice as measured by non-denaturing gel electrophoresis. When injected into C57BL/6 mice, these HDL "remnants" were rapidly converted to HDL 2 -sized lipoprotein particles, and were cleared from the plasma at a rate similar to HDL 2 . In assays in cultured cells, HDL remnants did not stimulate ATP-binding cassette transporter A1-dependent cholesterol efflux. When mixed with mouse plasma ex vivo, HDL remnants rapidly converted to larger HDL particles. These studies identify a previously ill-defined pathway in HDL metabolism, whereby SR-BI generates small, dense HDL particles that are rapidly remodeled in plasma. This remodeling pathway may represent a process that is important in determining the rate of apoA-I catabolism and HDL-mediated reverse cholesterol transport. Numerous epidemiological studies have indicated that HDL cholesterol (HDL-C) and apoA-I concentrations are inversely correlated to the risk for coronary heart disease. Consequently, much effort has been focused on the factors that regulate plasma HDL and apoA-I levels. Metabolic studies in humans have shown that variations in HDL-C and apoA-I concentrations are primarily associated with differences in the rate of apoA-I catabolism rather than apoA-I production (1-5). Many of the factors known to influence apoA-I catabolic rate have a major effect on the lipid composition of the HDL particle. For example, the accumulation of cholesterol ester (CE) in HDL (brought about in humans by a deficiency in CETP) is associated with delayed apoA-I catabolism (6). Conversely, LCAT deficiency, which results in a depletion of HDL CE, is associated with accelerated apoA-I catabolism (7). Accumulating evidence suggests that the kidney cortex is an important site for degrading lipid-poor apoA-I, perhaps through glomerular filtration followed by degradation in the proximal tubule. Cubilin, an endocytic receptor that is expressed on the apical surfaces of kidney proximal tubule cells, has been implicated in renal uptake of lipid-poor HDL (8, 9).Scavenger receptor class B type I (SR-BI) is an HDL receptor that mediates selective lipid uptake from receptor-bound HDL. During this process, CE is transferred from the core of the HDL particle to cells without the concomitant degradation of HDL apolipoproteins. Despite the fact that SR-BI mediates only CE uptake, liver-specific SR-BI o...

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“…In general, lipoprotein A-I is considered to be more protective against CHD than lipoprotein A-I:A-II. 33 Therefore, apoA-I levels may be a better marker for functional reverse cholesterol transport than HDL-C.…”

Section: Hdl Metabolism and Recurrent Cardiovascular Eventsmentioning

confidence: 99%

Apolipoprotein Concentrations During Treatment and Recurrent Coronary Artery Disease Events

Lennep

Westerveld

Lennep

et al. 2000

ATVB

141

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Abstract-The effect of untreated total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as cardiovascular risk factors in both primary and secondary prevention has been extensively investigated. The predictive value of on-treatment lipid and apolipoprotein levels on subsequent cardiovascular events is as yet uncertain. Eight hundred forty-eight patients (675 men and 173 women) with angiographically proven coronary artery disease (CAD) who received effective statin therapy (Ն30% decrease of baseline TC) were studied. We analyzed the predictive value of on-treatment levels of TC, LDL-C, triglycerides (TG), apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) on subsequent myocardial infarction (MI) and all cause mortality. On-treatment LDL-C levels were 2.55Ϯ0.55 mmol/L and 2.58Ϯ0.62 mmol/L for men and women respectively. Age-adjusted Cox regression analysis showed that only on-treatment apoA-I was predictive for future CAD events in both men and women, whereas on-treatment HDL-C was exclusively predictive in women. On-treatment apoB levels were predictive for recurrent CAD events in the total population but not after separate analysis for men and women. On-treatment levels of TC, LDL-C, and TG did not predict subsequent events. Multivariate analysis showed that on-treatment apoA-I and apoB were the only significant predictors for future cardiovascular events. On-treatment levels of TC, LDL-C, and TG were no longer associated with increased risk of recurrent cardiovascular events in CAD patients treated to target levels, which justifies the current guidelines. However, on-treatment levels of apoB and in particular apoA-I (and HDL-C in women) were significantly predictive for MI and all-cause mortality and may therefore be more suitable for cardiovascular risk assessment in this population. (Arterioscler Thromb Vasc

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Metabolism of high density lipoprotein subfractions

Cited by 42 publications

References 27 publications

Preβ high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice

Preβ high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice

The fate of HDL particles in vivo after SR-BI-mediated selective lipid uptake

Apolipoprotein Concentrations During Treatment and Recurrent Coronary Artery Disease Events

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