Abstract. Variants of apolipoprotein E (apoE) have been linked to lipoprotein glomerulopathy, a new glomerular disease characterized by the deposition of lipoproteins in mesangial capillaries. One third of affected patients are heterozygous for apoE2 Sendai (Arg145 Pro). Variants of apoE can also produce type III hyperlipoproteinemia (HLP). Recessive type III HLP is caused by apoE2 (Arg158 Cys), a mutant with diminished low-density lipoprotein (LDL) receptor binding but halfnormal heparin binding. Dominant type III HLP is caused by mutations that markedly alter heparin binding but modestly reduce receptor binding. This study examined whether apoE2 Sendai (Arg145 Pro) was functionally different from type III HLP-producing apoE variants by expressing apoE3, apoE2 (Arg158 Cys), apoE1 (Arg146 Glu), a dominant apoE variant, and apoE2 Sendai (Arg145 Pro) in the baculovirus system. LDL receptor binding was studied using recombinant apoE complexed to phospholipid vesicles and to very lowdensity lipoprotein from a patient with familiar apoE deficiency. Compared with apoE3, receptor-binding activities of apoE2 (Arg158 Cys), apoE1 (Arg146 Glu), and apoE2 Sendai (Arg145 Pro) all were less than 5%. Heparin-binding activities were 53%, 23%, and 66%, respectively, of apoE3. The distribution of apoE2 Sendai among the major plasma lipoprotein fractions was similar to that of apoE3 and apoE2 (Arg158 Cys). ApoE2 Sendai (Arg145 Pro) represents the only known mutation within the heparin-binding domain of apoE (residues 142 through 147), revealing diminished receptor binding and almost normal heparin binding. These unique characteristics of apoE2 Sendai (Arg145 Pro) may relate to the development of lipoprotein glomerulopathy.
Macrophage Infiltration into the Glomeruli in Lipoprotein Glomerulopathy