Key result
Human PON1 transgene expression significantly reduces atherosclerotic lesions in mouse models.
Answers are grounded in this paper and cite their sources.
BACKGROUND: Serum paraoxonase (PON1), an enzyme carried on HDL, inhibits LDL oxidation, and in human population studies, low PON1 activity is associated with atherosclerosis. In addition, PON1 knockout mice are more susceptible to lipoprotein oxidation and atherosclerosis. To evaluate whether PON1 protects against atherosclerosis and lipid oxidation in a dose-dependent manner, we generated and studied human PON1 transgenic mice. METHODS AND RESULTS: Human PON1 transgenic mice were produced by using bacterial artificial chromosome genomic clones. The mice had 2- to 4-fold increased plasma PON1 levels, but plasma cholesterol levels were unchanged. Atherosclerotic lesions were significantly reduced in the transgenic mice when both dietary and apoE-null mouse models were used. HDL isolated from the transgenic mice also protected against LDL oxidation more effectively. CONCLUSIONS: Our results indicate that PON1 protects against atherosclerosis in a dose-dependent manner and suggest that it may be a potential target for developing therapeutic agents for the treatment of cardiovascular disease.
No takes yet. Share an insight, caveat, or question.
Tward et al. (2002) studied Atherosclerosis. Human PON1 transgene expression vs. Non-transgenic dietary and apoE-null control mice was evaluated on Atherosclerotic lesion formation. Human PON1 transgene expression (yielding 2- to 4-fold higher plasma PON1 levels) significantly reduced atherosclerotic lesions in dietary and apoE-null mouse models.
Synapse has enriched 10 related papers. Consider them for comparative context: