Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to low density lipoprotein receptors.
It was previously reported that a protein-free microemulsion (LDE) with structure roughly resembling that of the lipid portion of low density lipoprotein (LDL) was presumably taken up by LDL receptors when injected into the bloodstream. In contact with plasma, LDE acquires apolipoproteins (apo) including apo E that would be the ligand for receptor binding. Currently, apo were associated to LDE by incubation with high density lipoprotein (HDL). LDE-apo uptake by mononuclear cells showed a saturation kinetics, with an apparent K(m) of 13.1 ng protein/mL. LDE-apo is able to displace LDL uptake by mononuclear cells with a Ki of 11.5 ng protein/mL. LDE without apo is, however, unable to displace LDL. The uptake of 14C-HDL is not dislocated by increasing amounts of LDE-apo, indicating that HDL and LDE-apo do not bind to the same receptor sites. In human hyperlipidemias, LDE labeled with 14C-cholesteryl ester behaved kinetically as expected for native LDL. LDE plasma disappearance curve obtained from eight hypercholesterolemic patients was markedly slower than that from 10 control normolipidemic subjects [fractional clearance rate (FCR) = 0.02 +/- 0.01 and 0.12 +/- 0.04 h-1, respectively; P < 0.0001]. On the other hand, in four severely hypertriglyceridemic patients, LDE FCR was not significantly different from the controls (0.07 +/- 0.03 h-1). These results suggest that LDE can be a useful device to study lipoprotein metabolism.
Maranhão
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RC
Heart Institute of the Medical School Hospital (Instituto do Coração do HC-FMUSP, São Paulo, Brazil. Sadler@opus.com.br
Roland
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IA
Toffoletto
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O
Ramires
J A
JA
Gonçalves
R P
RP
Mesquita
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CH
Pileggi
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F
D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000493:pharmacokinetics; D001667:Binding, Competitive; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters / Q000493:pharmacokinetics; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000378:metabolism; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism*
D001053:Apolipoproteins; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D004655:Emulsions; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL