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 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.
Department of Bioengineering, Imperial College, London, UK.
C Charles
CC
Michel
Cardiovascular Genetics Unit, University of Utah School of Medicine, Salt Lake City, UT.
M Nazeem
MN
Nanjee
Department of Surgical Research and Transplantology, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Waldemar L
WL
Olszewski
Magdalen College, University of Oxford, Oxford, UK.
Norman E
NE
Miller
D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood / Q000378:metabolism; D001692:Biological Transport; D004058:Diffusion; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000378:metabolism*; D008875:Middle Aged; D014462:Ultrafiltration; D055815:Young Adult
D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL
high density lipoprotein; low density lipoprotein; transcytosis