Heterogeneity of human high density lipoprotein: Presence of lipoproteins with and without apoE and their roles as substrates for lecithin:cholesterol acyltransferase reaction

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RESUMO

By affinity chromatography on heparin-Sepharose, two classes of lipoproteins were separated from high density lipoproteins (HDL) isolated from patients with primary or secondary lecithin:cholesterol acyltransferase (LCATase; EC 2.3.1.43) deficiency and from normal subjects. The unretained fraction, HDLA, was characterized by having apoA-I as a major apoprotein; it also contained apoA-II, -C-II, and -C-III but it contained only traces of immunodetectable apoE and no apoB. The retained fraction, HDLE, had apoE as the major apoprotein; it also contained apoA-I, -A-II, -B, -C-II, and -C-III. The relative concentration of apoA-I increased with increasing density in the HDLE subclass. Compared to HDLA, HDLE had a significantly higher cholesterol content and a lower protein concentration. HDLE was mainly (90%) contained within the HDL2 subfraction. Contamination of HDLE by low density lipoproteins (LDL) or Lp(a) was minimal on the basis of pre-β-electrophoretic mobility and absence of albumin, respectively. Contamination by LDL or Lp(a) could be resolved in part by application of HDLE to concanavalin A-Sepharose or to heparin-Sepharose with a shallow gradient. When evaluated as substrates for a highly purified LCATase preparation, the initial reaction rates and Vmax obtained with HDLA were always higher than those obtained with HDLE in any given plasma. However, both HDL subclasses from LCATase-deficient subjects were better substrates than the corresponding HDL subclasses from normal plasma. Also, both HDL3A and HDL3E isolated from normal HDL3 were better substrates than the corresponding subclasses isolated from normal HDL2. The recognition of this compositional and functional heterogeneity within HDL will allow a better understanding of the metabolism of this lipoprotein class.

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