Relevance of different apolipoprotein content in binding of homocysteine to plasma lipoproteins

Background and Aims: In plasma the atherogenic thiol homocysteine (Hcy) circulates either free or bound to proteins (Pb-Hcy). The present study sets out to evaluate the lipoprotein-Hcy (LP-Hcy) binding in vivo and the possible influence of different apolipoprotein content in this binding, being lipoprotein oxidation a possible mechanism of Hcy-induced damage. Methods and Results: In 34 healthy subjects we assayed fasting plasma lipoprotein and correspondent apolipoprotein (apo A-I, apo A-II, apo C-II, apo C-III, apo B, apo(a) and apo E content, and Hcy bound to different plasma protein fractions; moreover ten subjects underwent an oral methionine load in order to evaluate possible dynamic modifications of Pb-Hcy and LP-Hcy after induction of hyperhomocysteinemia. Pb-Hcy (mean values 9.22+/-1.7 mumol/L) represented about 78% of total plasma Hcy (mean values 11.8+/-1.8 mumol/L). Pb-Hcy distribution between the different fractions was as follows (mumol/L): VLDL = 0.25+/-0.08 (2.7%); LDL = 0.88+/-0.22 (9.5%);HDL = 1.40+/-0.36 (15.2%);fractions with density greater than 1.21 g/mL (Lipoprotein-Free Protein Fraction, LPDS) = 6.7+/-1.2 (72.6%). Hcy/protein ratios (nmol/mg of protein) in each protein fraction were: VLDL = 0.32+/-0.19, LDL = 0.43+/-0.37, HDL = 0.26+/-0.18, LPDS < 0.1, thus suggesting a higher binding capacity for Hcy by VLDL and LDL. These data were confirmed by the higher increase in Hcy content in LDL and VLDL (76 and 90%, respectively vs 36% and 3.1% for HDL and LPDS fractions) after hyperhomocysteinemia. Lp-Hcy binding significantly correlated with the apo B content of VLDL and LDL and Apo A-I content of HDL. Conclusions: An important fraction of plasma Hcy circulates bound to LP (about 27% of Pb-Hcy); VLDL and LDL show the highest binding capacity for Hcy, probably due to their content in Apo B, a possible high capacity binding site for Hcy. (C)2003, Medikal Press.