Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice.

Abstract:

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.

journal_name

Circulation

journal_title

Circulation

authors

Tward A,Xia YR,Wang XP,Shi YS,Park C,Castellani LW,Lusis AJ,Shih DM

doi

10.1161/01.cir.0000023623.87083.4f

subject

Has Abstract

pub_date

2002-07-23 00:00:00

pages

484-90

issue

4

eissn

0009-7322

issn

1524-4539

journal_volume

106

pub_type

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