Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to low density lipoprotein...

Area of Science:

• Biochemistry
• Lipid Metabolism
• Pharmacology

Background:

• Lipoprotein-depleted emulsions (LDE) structurally resemble the lipid core of low-density lipoprotein (LDL).
• LDE are hypothesized to be internalized via LDL receptors after acquiring apolipoproteins (apo) from plasma, particularly apo E.

Purpose of the Study:

• To investigate the uptake mechanism and metabolic fate of LDE in vitro and in vivo.
• To assess the potential of LDE as a model system for studying lipoprotein metabolism, especially in hyperlipidemic conditions.

Main Methods:

• Assessing LDE-apo uptake kinetics and competition with LDL in mononuclear cells.
• Investigating the binding specificity of LDE-apo by examining high-density lipoprotein (HDL) uptake.
• Administering radiolabeled LDE to hypercholesterolemic and hypertriglyceridemic patients and healthy controls to determine plasma clearance rates.

Main Results:

• LDE-apo exhibited saturation kinetics in mononuclear cell uptake, with an apparent K(m) of 13.1 ng protein/mL.
• LDE-apo displaced LDL uptake (Ki = 11.5 ng protein/mL), but LDE without apo did not.
• LDE-apo did not affect 14C-HDL uptake, indicating distinct receptor binding.
• In hypercholesterolemic patients, LDE plasma disappearance was significantly slower (FCR = 0.02 h-1) compared to controls (FCR = 0.12 h-1).
• In hypertriglyceridemic patients, LDE clearance was not significantly different from controls (FCR = 0.07 h-1).

Conclusions:

• LDE, upon acquiring apolipoproteins, interacts with the LDL receptor pathway.
• The altered plasma clearance of LDE in hypercholesterolemia highlights its utility in studying lipoprotein disorders.
• LDE serves as a promising tool for investigating lipoprotein metabolism and receptor-mediated uptake mechanisms.