Lipoprotein lipase compensates for the defective function of apo E variants in vitro by interacting with proteoglycans and lipoprotein receptors.
Lipoprotein lipase (LPL) and apolipoprotein E (apo E) independently enhance binding and uptake of lipoproteins to cells. A coordinate effect of LPL and apo E has been previously described in human hepatozytes where simultaneous addition of both proteins resulted in an additive increase of chylomicron binding and uptake. The role of lipoprotein receptors and proteoglycans in this coordinate effect was now analysed using various cell types and heparinase treatment. To investigate a pathophysiological relevance, the effect of LPL and normal apo E-3 was compared to LPL and four apo E variants, associated with type III hyperlipoproteinemia (HLP). Apo E-3 and LPL increased the binding and uptake of chylomicrons and beta-very low density lipoproteins (VLDL) in an additive way in all cell types analysed, except proteoglycan deficient Chinese hamster ovary (CHO)-cells. Heparinase treatment almost completely abolished the effect of apo E and LPL. Addition of LPL to the apo E variants resulted in significant compensation of their defective function in mediating beta-VLDL binding to low density lipoprotein (LDL)-receptor defective fibroblasts. These findings indicate that the coordinate effect of apo E and LPL is mediated by proteoglycans and lipoprotein receptors, independent of the LDL receptor. LPL may compensate for the defective function of apo E variants by enhancing lipoprotein binding to these receptors. Defects in this mechanism may explain how mutations in the LPL molecule contribute to the manifestation of type III HLP in addition to the presence of a defective apo E.
Mann
W A
WA
Medical Clinic, University Hospital Eppendorf, Hamburg, Germany. mann@uke.uni-hamburg.de
Meyer
N
N
Berg
D
D
Greten
H
H
Beisiegel
U
U
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D016466:CHO Cells; D002914:Chylomicrons / Q000378:metabolism; D006224:Cricetinae; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental; D011509:Proteoglycans / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000378:metabolism*
D001057:Apolipoproteins E; D002914:Chylomicrons; D008079:Lipoproteins, VLDL; D011509:Proteoglycans; D018110:Receptors, Lipoprotein; D008071:Lipoprotein Lipase