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Toxicity of enzymically-oxidized low-density lipoprotein
A W Bernheimer1, W G Robinson, R Linder
1Department of Microbiology, New York University Medical Center, NY 10016.
Biochemical and Biophysical Research Communications
|October 14, 1987
Summary
Cholesterol oxidase injection is lethal to hyperlipidemic rabbits but not normal ones. This is because oxidized low-density lipoprotein becomes toxic, potentially initiating human atherosclerosis.
Area of Science:
- Biochemistry
- Cardiovascular Science
- Cell Biology
Background:
- Hyperlipidemia and atherosclerosis are significant cardiovascular concerns.
- Low-density lipoprotein (LDL) is implicated in atheroma formation.
- The role of LDL cholesterol oxidation in atherogenesis requires further elucidation.
Purpose of the Study:
- To investigate the effects of cholesterol oxidase on hyperlipidemic and normal rabbits.
- To determine the cytotoxicity of enzymatically oxidized LDL.
- To explore the potential role of LDL cholesterol oxidation in initiating human atheromatous lesions.
Main Methods:
- Intravenous injection of cholesterol oxidase into rabbits with diet-induced hyperlipidemia and normal rabbits.
- Treatment of LDL with cholesterol oxidase.
- Assessment of cytotoxicity of oxidized LDL on human cell lines and bovine aortic endothelial cells.
Main Results:
- Cholesterol oxidase injection was lethal to hyperlipidemic rabbits but not normal rabbits.
- Cholesterol oxidase-treated LDL killed normal rabbits, unlike untreated LDL.
- Enzymatically oxidized LDL exhibited cytotoxicity towards human and bovine cell lines.
Conclusions:
- In vivo conversion of LDL cholesterol to cholestenone by cholesterol oxidase may be lethal in hyperlipidemic states.
- Enzymatically oxidized LDL is cytotoxic.
- This process may contribute to the initiation of human atheromatous lesions.