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


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.
Ventura
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P
University of Modena and Reggio Emilia, Department of Internal Medicine, Chair of Internal Medicine II, via del Pozzo 71, 41100 Modena, Italy. paoloven@unimore.it
Panini
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R
Rosa
M C
MC
Gaetti
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E
Salvioli
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D001053:Apolipoproteins / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D006710:Homocysteine; D002784:Cholesterol