title: S-homocysteinylated LDL apolipoprotein B adversely affects human endothelial cells in vitro.
abstract: OBJECTIVE
  In recent years elevated homocysteine (Hcy) levels have been widely recognized as a risk factor for cardiovascular diseases (CVDs) and a connection between hyperhomocysteinemia and lipid metabolism has been suggested to have a possible role in endothelial vascular damage as lipoprotein fractions contain higher Hcy levels in hypercholesterolemia, compared to normolipidemic individuals. However, the biochemical events underlying the interaction between Hcy and LDL are still poorly understood.
  
  
  RESULTS
  Herein we have investigated the interaction of LDL with Hcy by measuring thiols S-linked to apoprotein using capillary electrophoresis and have evaluated the effect of S-homocysteinylated LDL on human endothelial cells (HECs). We found that Hcy binds to LDL in a dose dependent manner and the saturation binding is achieved at 100 micromol/L Hcy in about 5h. Addition of Hcy resulted in a rapid displacement of other thiols bound to apoprotein and this was dependent on the concentration of Hcy added. For the first time we also demonstrated that treatment of HECs with homocysteine-S-LDL (Hcy-S-LDL) resulted in the induction of significantly higher levels of reactive oxygen species (ROS) compared to N-LDL (native LDL). Furthermore, the Hcy-S-LDL-induced a rise in intracellular ROS production was followed by a marked reduction of HECs proliferation and viability.
  
  
  CONCLUSIONS
  Although the mechanism by which Hcy-S-LDL elicits the current cellular effects needs further investigation, our data suggest that intracellular ROS production induced by Hcy-S-LDL might be responsible for the observed HECs damage and indicate that Hcy-S-LDL may have some role in CVD.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, Sassari, Italy. angelozinellu@libero.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Zinellu
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sotgia
authors.forename: Bastianina
authors.initials: B
authors.lastname: Scanu
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pintus
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Posadino
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cossu
authors.forename: Luca
authors.initials: L
authors.lastname: Deiana
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sengupta
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Carru
mesh_terms: D001055:Apolipoproteins B / Q000378:metabolism / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D017382:Reactive Oxygen Species; D006710:Homocysteine