Identification of a distinct human high‐density lipoprotein subspecies defined by a lipoprotein‐associated protein, K‐45

Abstract

In an attempt to provide immunological tools for subfractionation of high‐density lipoproteins (HDL), monoclonal antibodies were raised against HDL complexes. Two clones identified a peptide, provisionally named K‐45 (pI 4.5–4.9; molecular mass 45 kDa, range 42–48 kDa), whose plasma distribution and lipoprotein association were fully characterised. Gel filtration localised the peptide to the HDL region of human plasma where it co‐eluted with apolipoprotein (apo) A‐I, the structural protein of HDL. Complementary studies employing immunoabsorption with anti‐(apo A‐I) antibodies removed 90% of K‐45 from plasma: conversely, anti‐(apo A‐II) antibodies eliminated only 10% of K‐45. Immunoaffinity chromatography on an anti‐(K‐45) column revealed that the peptide was present in a distinct. HDL subspecies containing three major proteins: K‐45, apo A‐I and clusterin or apo J. The lipoprotein nature of the bound fraction was indicated by electron microscopy (diameter 9.6 ± 3.3 nm) and quantification of lipids, the latter showing an unusually high triacyglycerol concentration. Plasma concentrations of K‐45 were positively correlated with apo A‐I and HDL‐cholesterol and negatively correlated with apo B and total cholesterol. Thus, the peptide appears to be linked, directly or indirectly, to processes which give rise to an anti‐atherogenic lipid profile. After completion of the present studies, an N‐terminal sequence identical to that of K‐45 was reported in recently isolated cDNA clones. These clones encode paraxonasc.