GENDER EFFECTS ON THE DISTRIBUTION OF THE CHOLESTERYL ESTER TRANSFER PROTEIN IN APOLIPOPROTEIN A-I-DEFINED LIPOPROTEIN SUBPOPULATIONS

Two subpopulations of apolipoprotein A-I-containing lipoproteins, thos e containing only apoA-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I/A-II), were isolated by immunoaffinity chromatography o f plasma from 44 subjects, comprising four groups (male or female, wit h or without hyperlipidemia. ApoA-I-defined particles (LpAs) were asse ssed for their content of cholesteryl ester transfer protein (CETP) an d for their ability to act as substrates for CETP. Although plasma CET P concentration was similar in all groups, the plasma concentration of LpA-I-associated CETP was significantly higher in females than in mal es (1.56 +/- 0.11 versus 0.93 +/- 0.13 mg/l, P < 0.05). In females, th e major fraction of CETP was found in LpA-I, whereas in normolipidemic males CETP was evenly distributed between LpA-I and LpA-I/A-II, and i n hyperlipidemic males the majority of CETP was found in LpA-I/A-II. I n all groups, the percentage of CETP in LpA-I was correlated with the concentration of apoA-I in LpA-T (r = 0.64, P < 0.001). Native gradien t gel electrophoresis of isolated LpAs showed that gradient gel electr ophoresis of isolated LpAs showed that CETP was broadly distributed wi thin different sized particles. LpA-I and LpA-I/A-II showed similar ef ficiency of CETP-mediated cholesteryl eater exchange with LDL. In conc lusion, even though LpA-I has a much higher apparent affinity for CETP than LpA-I/A-II, both LpAs can bind CETP and act as equivalent CETP s ubstrates in vitro. Thus, in subjects with low levels of LpA-I (notabl y hyperlipidemic males), most of the plasma neutral lipid exchange wil l involve LpA-I/A-II. This could be a factor contributing to a general impairment in reverse cholesterol transport in subjects with low LpA- I.