Effects of estrogenic oral contraceptives on the lipoprotein B particle system defined by apolipoproteins E and C-III content

Apolipoproteins E and C-III are modulators of lipoprotein metabolism that c ould affect development of atherosclerosis, The prevalence in plasma of apo B-containing particles (LpB) that contain either apoE or apoC-III, both or neither, and the effect of estrogen on these lipoproteins are unknown. The LPB particle system, defined by the presence or absence of apoE or C-III, w as studied in 13 normolipidemic women, 7 nonusers and 6 users of oral contr aceptives. Fasting plasma was separated by anti-apoE and C-III affinity chr omatography and ultracentrifugation into four types of VLDL, IDL, and LDL p articles: with apoE but not apoC-III (E+C-), apoC-III but not apoE (E-C+), both (E+C+) or neither (E-C-), The predominant VLDL particles were E-C- (42 % in nonusers, 56% in users) and E+C+ (39% in nonusers, 24% in users), sugg esting that apoE and apoC-III mainly exist together in VLDL, In IDL, E-C- w as the major fraction (74% nonusers, 81% users), and in LDL, it was 99% in both groups. The triglycerides in VLDL and IDL were mainly contained in Cparticles (79% and 66% of the total VLDL and IDL triglycerides, respectivel y), Within VLDL, IDL, and LDL, E-C- particles had the smallest size and E+C + or E-C+ the largest, Users had higher concentrations of VLDL E-C- (280%) and IDL E-C- (90%) particles than nonusers. They also had higher free chole sterol and cholesteryl ester concentrations associated with these fractions and with VLDL E-C+. The triglyceride contents of VLDL E-C- particles were lower in users of oral contraceptives than in nonusers. This study demonstr ates that the elevated VLDL TG concentrations in users of estrogen-dominant oral contraceptives is mainly caused by an increased concentration of smal l VLDL particles that have reduced TG content, and that do not have apoE an d C-III. These particles may have lower atherogenicity than particles enric hed with apoE and C-III.