title: Factors affecting S-homocysteinylation of LDL apoprotein B.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Biomediche, Cattedra di Biochimica Clinica, Università degli Studi di Sassari, Sassari, Italy. angelozinellu@libero.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Zinellu
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Zinellu
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sotgia
authors.forename: Marilena
authors.initials: M
authors.lastname: Formato
authors.forename: Gian Mario
authors.initials: GM
authors.lastname: Cherchi
authors.forename: Luca
authors.initials: L
authors.lastname: Deiana
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Carru
mesh_terms: 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
chemical_list: D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D013438:Sulfhydryl Compounds; D006710:Homocysteine