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Published on: October 12, 2017
S-homocysteinylated LDL apolipoprotein B adversely affects human endothelial cells in vitro
Angelo Zinellu1, Salvatore Sotgia, Bastianina Scanu
1Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, Sassari, Italy. angelozinellu@libero.it
Insights
Elevated homocysteine (Hcy) binds to LDL, increasing oxidative stress and damaging endothelial cells. This homocysteine-S-LDL interaction may contribute to cardiovascular disease development.
Area of Science:
- Biochemistry
- Cardiovascular Science
- Cell Biology
Background:
- Elevated homocysteine (Hcy) is a known cardiovascular disease (CVD) risk factor.
- Hyperhomocysteinemia is linked to lipid metabolism and endothelial damage.
- The interaction between Hcy and low-density lipoprotein (LDL) is not well understood.
Purpose of the Study:
- To investigate the biochemical interaction between Hcy and LDL.
- To evaluate the effects of Hcy-modified LDL on human endothelial cells (HECs).
Main Methods:
- Investigated Hcy-LDL interaction by measuring thiols linked to apoprotein.
- Utilized capillary electrophoresis for thiol analysis.
- Assessed the impact of S-homocysteinylated LDL on HECs.
Main Results:
- Hcy binds to LDL in a dose-dependent manner, reaching saturation at 100 micromol/L.
- Hcy displaces other thiols bound to apoprotein.
- Treatment with Hcy-S-LDL significantly increased reactive oxygen species (ROS) in HECs.
- Hcy-S-LDL reduced HEC proliferation and viability.
Conclusions:
- Hcy-S-LDL induces intracellular ROS production, potentially causing HEC damage.
- Hcy-S-LDL may play a role in the pathogenesis of cardiovascular diseases.
- Further research is needed to elucidate the precise mechanisms.
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.
Methods And 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.
