Modulation of apolipoprotein E-mediated plasma clearance and cell uptake of emulsion particles by cholesteryl ester.
Cholesteryl ester, along with triglyceride (TG), is the major core component of plasma lipoproteins. We investigated the effect of core composition on the physical state and metabolic behavior of lipid emulsions, as model particles of lipoproteins. Fluorescence studies using 1,6-diphenylhexatriene analogs showed that although cholesteryl oleate (CO) significantly decreased core mobility, the surface rigidity of phosphatidylcholine (PC) monolayers was independent of core composition. When intravenously injected into rats, the increased amount of core CO tended to retard TG emulsion removal from plasma, and the initial clearance rate was correlated with the amount of apolipoprotein E (apoE) bound from plasma. In addition, PC liposomes with a similar emulsion particle size showed negligible binding of apoE and were cleared at a slower rate compared to all emulsions. Furthermore, the effect of CO on the binding behavior of apoE to the emulsion surface and the emulsion uptake by hepatocytes was assessed in vitro. Replacing core TG with CO was found to decrease the apoE binding capacity to emulsions markedly without changing the binding affinity and thereby to reduce the cell uptake of emulsion particles by HepG2 cells. These results indicate that the physical state of core lipids, which can be modulated by CO content, plays a role in emulsion metabolism through the alteration in apoE binding.
Saito
H
H
National Institute of Health Sciences, Osaka , Japan.
Okuhira
K
K
Tsuchimoto
N
N
Vertut-Doi
A
A
Matsumoto
C
C
Tanimoto
T
T
Okada
S
S
Handa
T
T
D001057:Apolipoproteins E / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D002788:Cholesterol Esters / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D004161:Diphenylhexatriene; D004655:Emulsions / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D005454:Fluorescence Polarization; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D010316:Particle Size; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D014304:Triolein
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D004655:Emulsions; D014280:Triglycerides; D014304:Triolein; D004161:Diphenylhexatriene; C014409:cholesteryl oleate