Oxidized LDL Stimulates Lipid Peroxidation-derived DNA and Protein Adducts in Human Vascular Endothelial and Smooth Muscle Cells

【摘要】 Oxidized low density lipoprotein(ox LDL) can trigger intracellular production of reactive oxygen species and lipid peroxidation(LPO), and is thought to contribute to initiation and progression of atherosclerosis. In order to understand the correlation between ox LDL and macromolecular damage, we measured levels of LPO-derived miscoding etheno-DNA adducts and LPO-modified proteins in cultured human vascular endothelial and smooth muscle cells after incubation with ox LDL for up to 48 h. A semi-quantative analysis method for 1, N6-ethenodeoxyadenosine(εd A) by immunohistochemistry was applied. After ox LDL stimulation, εd A-stained nuclei were significantly increased in both endothelial and smooth muscle cells. Similarly, 4-hydroxy-2-nonenal(4-HNE)-modified proteins, as analyzed by immunohistochemistry and Western blotting, were also 3–5 fold increased. It was concluded LPO-derived etheno-DNA adducts and LPO-modified proteins are strongly induced by ox LDL in human vascular endothelial and smooth muscle cells. This macromolecular damage may contribute to the dysfunction of arterial endothelium and the onset of atherosclerosis.更多还原

【Abstract】 Oxidized low density lipoprotein(ox LDL) can trigger intracellular production of reactive oxygen species and lipid peroxidation(LPO), and is thought to contribute to initiation and progression of atherosclerosis. In order to understand the correlation between ox LDL and macromolecular damage, we measured levels of LPO-derived miscoding etheno-DNA adducts and LPO-modified proteins in cultured human vascular endothelial and smooth muscle cells after incubation with ox LDL for up to 48 h. A semi-quantative analysis method for 1, N6-ethenodeoxyadenosine(εd A) by immunohistochemistry was applied. After ox LDL stimulation, εd A-stained nuclei were significantly increased in both endothelial and smooth muscle cells. Similarly, 4-hydroxy-2-nonenal(4-HNE)-modified proteins, as analyzed by immunohistochemistry and Western blotting, were also 3–5 fold increased. It was concluded LPO-derived etheno-DNA adducts and LPO-modified proteins are strongly induced by ox LDL in human vascular endothelial and smooth muscle cells. This macromolecular damage may contribute to the dysfunction of arterial endothelium and the onset of atherosclerosis.更多还原