Variations in lipid and apolipoprotein concentrations in human leg lymph: effects of posture and physical exercise

Cooke, C. Justin; Nanjee, M. Nazeem; Stepanova, I. P.; Olszewski, Waldemar L.; Miller, N. E.

doi:10.1016/j.atherosclerosis.2003.07.004

Cited by 29 publications

(26 citation statements)

References 14 publications

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“…We endeavored to achieve steady state conditions by keeping the subjects supine for at least 8 h prior to the samples being taken. When Cooke et al ( 55 ) measured lymph and plasma concentrations of albumin and apos in nine subjects over 4 days under conditions similar to those in the present study, lymph apo B concentration became constant shortly before midnight and remained so until 8:00 AM, when activity resumed. Furthermore, the rate at which lymph protein concentrations reach steady-state values following changes in microvascular fl uid fi ltration should be inversely related to their volumes of distribution in the interstitial fl uid.…”

Section: Discussionmentioning

confidence: 93%

LDL and HDL transfer rates across peripheral microvascular endothelium agree with those predicted for passive ultrafiltration in humans

Michel

Nanjee

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org chylomicrons and VLDLs, are limited in distribution to blood and metabolized at the luminal surface of vascular endothelium by lipoprotein lipase. By contrast, the LDLs and HDLs move between plasma and interstitial fl uid as they transport lipids to and from different cell types. Each LDL particle contains a single molecule of apoB100 (apo B) ( 1, 2 ). The principal protein component of all HDL particles is apo AI, which usually accounts for about 70% of total HDL protein mass. Some HDLs also contain apo AII as the second most abundant protein ( 3 ). Studies of human afferent peripheral lymph have shown that the concentrations of apo AI and apo AII in normal human interstitial fl uid average about one-fi fth of those in plasma ( 4-6 ), while lymph apo B concentration averages only one-tenth ( 4, 7 ). The ratio of HDL to LDL particles in interstitial fl uid has been estimated to average about 50:1 in healthy humans ( 4,8 ).The striking differences in lipoprotein concentrations between plasma and interstitial fl uid, combined with their roles in atherosclerosis, highlight the importance of understanding the mechanisms by which they move into and out of the extravascular compartment. By analyzing data on adipokines of different molecular size, Miller et al. ( 9 ) showed that the principal pathway by which a macromolecule leaves the interstitium of peripheral tissues in humans is determined by its size, the proportion leaving via capillaries decreasing and that via the lymphatic system increasing, as molecular radius rises. As proteins of radius у 3.2 nm were found to leave entirely in lymph, it is reasonable to assume that this applies also to LDL and HDL, given that their radii greatly exceed this fi gure ( 10,11 ). This interpretation agrees with recent studies of HDL transport via the lymphatic system in mice ( 12 ).The mechanisms by which HDL and LDL are transported from plasma into interstitial fl uid are not understood. Two

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Section: Discussionmentioning

confidence: 93%

LDL and HDL transfer rates across peripheral microvascular endothelium agree with those predicted for passive ultrafiltration in humans

Michel

Nanjee

et al. 2015

Journal of Lipid Research

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“…Accordingly, human peripheral lymph contains HDL-C (12)(13)(14), and estimates indicate a lymph transport of more than 300 mg per day (15). Placed into the context of estimates of overall neutral and acidic sterol excretion per day per kilogram in humans (16), the flux through lymph could represent a substantial pathway for removal of cholesterol from tissues body wide.…”

Section: Introductionmentioning

confidence: 99%

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

Martel¹,

Li²,

Fulp³

et al. 2013

J. Clin. Invest.

288

314

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Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin -1 surgical and the other genetic -to quantitatively track RCT following injection of [ 3 H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [ 2 H] 6 -labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [ 2 H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

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“…Under such conditions, the flux of a macromolecule to IF is linearly related to its concentration in plasma (15,28). We have shown that, at a constant flow rate (e.g., samples collected at the same time of day, or under standardized conditions of posture and physical exercise), the concentration of apoA-I in lymph is directly related to its concentration in plasma (8,13).…”

Section: Discussionmentioning

confidence: 95%

“…Such circadian variations occur in all lymph protein concentrations in ambulant subjects, as a consequence of the alterations in lymph flow rate (i.e., IF production rate) that are pro- duced by changes in posture and physical activity (13,15). The amplitude of the fluctuation varies from protein to protein as a function of molecular size.…”

Section: Discussionmentioning

confidence: 99%

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Mass kinetics of apolipoprotein A-I in interstitial fluid after administration of intravenous apolipoprotein A-I/lecithin discs in humans

Hovorka

Nanjee

Cooke

et al. 2006

Journal of Lipid Research

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Apolipoprotein kinetics are customarily determined by modeling time curves of specific radioactivity or isotopic enrichment in plasma after intravenous infusion of radiolabeled lipoproteins or stable isotope-enriched amino acids. However, this provides no information on the fractional rate of transfer of the apolipoprotein from plasma to interstitial fluid (k p-if ) or its mean residence time in interstitial fluid (MRT if ). To determine these parameters for a pharmacologic dose of exogenous apolipoprotein A-I

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Variations in lipid and apolipoprotein concentrations in human leg lymph: effects of posture and physical exercise

Cited by 29 publications

References 14 publications

LDL and HDL transfer rates across peripheral microvascular endothelium agree with those predicted for passive ultrafiltration in humans

LDL and HDL transfer rates across peripheral microvascular endothelium agree with those predicted for passive ultrafiltration in humans

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

Mass kinetics of apolipoprotein A-I in interstitial fluid after administration of intravenous apolipoprotein A-I/lecithin discs in humans

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