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

The mechanisms by which LDLs and HDLs cross the vascular endothelium from plasma into interstitial fluid are not understood, and have never been studied in humans in vivo. We determined whether the plasma-to-lymph clearance rates of LDL and HDL conform with those predicted by passive ultrafiltration...

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Bibliographic Details
Published in:Journal of lipid research 2015-01, Vol.56 (1), p.122-128
Main Authors: Michel, C. Charles, Nanjee, M. Nazeem, Olszewski, Waldemar L., Miller, Norman E.
Format: Article
Language:English
Subjects:
Adult
Aged
Apolipoproteins - blood
Apolipoproteins - metabolism
Biological Transport
Diffusion
Endothelium, Vascular - metabolism
high density lipoprotein
Humans
Lipoproteins, HDL - blood
Lipoproteins, HDL - metabolism
Lipoproteins, LDL - blood
Lipoproteins, LDL - metabolism
low density lipoprotein
Lymph - metabolism
Male
Microvessels - metabolism
Middle Aged
transcytosis
Ultrafiltration
Young Adult
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Summary:The mechanisms by which LDLs and HDLs cross the vascular endothelium from plasma into interstitial fluid are not understood, and have never been studied in humans in vivo. We determined whether the plasma-to-lymph clearance rates of LDL and HDL conform with those predicted by passive ultrafiltration through intercellular pores, or if it is necessary to invoke an active process such as receptor-mediated transcytosis. Plasma and afferent peripheral lymph were collected under steady-state conditions from 30 healthy men, and assayed for seven globular proteins of molecular radii 2.89–8.95 nm, complement C3, and apo AI, apo AII, and apo B. Plasma-to-lymph clearance rates of the seven proteins fitted the relation expected for molecules of their size when transported through two populations of pores of radius 4.95 and 20.1 nm. The same model parameters were then found to accurately predict the clearance rates of both HDL and LDL. The apparent clearance of complement C3, previously shown to be secreted by cultured endothelium, exceeded that predicted by the model. We conclude that the transport of HDL and LDL from plasma into interstitial fluid across the peripheral vascular endothelium in healthy humans can be explained by ultrafiltration without invoking an additional active process such as transcytosis.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M055053