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Clinical Chemistry 52: 2054-2059, 2006. First published September 21, 2006; 10.1373/clinchem.2006.071142
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Right arrow Lipids, Lipoproteins, and Cardiovascular Risk Factors
(Clinical Chemistry. 2006;52:2054-2059.)
© 2006 American Association for Clinical Chemistry, Inc.

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Factors Affecting S-Homocysteinylation of LDL Apoprotein B

Angelo Zinellu1,a, Elisabetta Zinellu2, Salvatore Sotgia1, Marilena Formato2, Gian Mario Cherchi2, Luca Deiana1 and Ciriaco Carru1,a

1 Dipartimento di Scienze Biomediche, Cattedra di Biochimica Clinica, and 2 Dipartimento di Scienze Fisiologiche, Biochimiche e Cellulari, Università degli Studi di Sassari, Sassari, Italia.

aAddress correspondence to these authors at: Chair of Clinical Biochemistry, Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy. Fax 39-079228120; e-mail angelozinellu{at}libero.it (A.Z.), carru{at}uniss.it (C.C.).

Background: Hyperhomocysteinemia is an important risk factor for vascular disease and atherosclerosis, but the mechanisms by which homocysteine exerts its deleterious effects are not known. Because oxidation and/or homocysteinylation may increase atherogenicity of LDL, we investigated S-homocysteinylation of LDL as a possible contributor to atherosclerosis pathogenesis.

Methods: We used capillary electrophoresis to measure LDL-bound thiols [homocysteine, cysteine (Cys), cysteinylglycine, glutathione, and glutamylcysteine] in 104 healthy study participants We also assessed total plasma thiol concentrations and lipid profiles.

Results: Our data suggest that apoprotein B (apoB)-cysteinylglycine (CysGly), apoB-Hcy, and apoB-Cys concentrations are markedly higher in men than in women. The percentage of CysGly and glutathione on apoB was higher than that of the same thiols in plasma, whereas the other thiols were markedly less prevalent in lipoprotein than in plasma. Pearson correlation showed that among all thiols, only total plasma Hcy is related to apoB-Hcy concentrations. Multiple correlation analysis confirmed that total Hcy was the most important determinant of apoB-Hcy. Age and LDL cholesterol also showed positive associations, but Cys and, mainly, CysGly were negatively associated with apoB-Hcy concentrations.

Conclusions: apoB-Hcy derivative formation is mainly dependent on total homocysteine concentration. Increased cholesterol concentrations are related to increased apoB-Hcy. CysGly seems to compete with Hcy for binding to LDL apoprotein, suggesting that CysGly may protect against atherosclerosis by decreasing the concentrations of Hcy transferred by LDL from plasma to endothelial and subendothelial spaces.






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