Chylomicron remnant metabolism in human apolipoprotein E isoform specific transgenic mice and apo E isoform related Aß metabolism in cells

In man, apo E is expressed as 3 common isoforms E2, E3 and E4. Chylomicrons and their remnants (CR) are cleared rapidly from plasma by the liver by a process requiring apo E for binding to the low density lipoprotein receptor and other receptors. In vivo studies in mice show that the metabolism of CR was markedly increased when compared with either human apo E2, E3 or E4 transgenic mice indicating that mouse apo E is essential for the metabolism of remnant-like emulsions in mice. In vitro studies indicate binding of emulsion remnants to Hep G2 cells was less with recombinant apo E2 when compared with apo E3 or apo E4 isoforms. When apo E isoforms were derived from an E.coli expression system the binding of CR was less when compared with baculovirus derived apo E isoforms. Recombinant apo E2 (Arg136->Cys) was found to bind poorly to Hep G2 cells. Our results show that apo E3 and apo E4 but not apo E2 were essential for the binding, uptake and metabolism of CR with mouse apo E more important than human apo E in CR metabolism with the involvement of Aß peptide in apo E remnant-like emulsion metabolism in cells.