Factors affecting S-homocysteinylation of LDL apoprotein B.
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.
Zinellu
Angelo
A
Dipartimento di Scienze Biomediche, Cattedra di Biochimica Clinica, Università degli Studi di Sassari, Sassari, Italy. angelozinellu@libero.it
Zinellu
Elisabetta
E
Sotgia
Salvatore
S
Formato
Marilena
M
Cherchi
Gian Mario
GM
Deiana
Luca
L
Carru
Ciriaco
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood* / Q000737:chemistry; D005260:Female; D006710:Homocysteine / Q000097:blood* / Q000737:chemistry; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012307:Risk Factors; D012737:Sex Factors; D013438:Sulfhydryl Compounds / Q000097:blood* / Q000737:chemistry
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D013438:Sulfhydryl Compounds; D006710:Homocysteine