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Paraoxonase, a cardioprotective enzyme: continuing issues
Godfrey S Getz1, Catherine A Reardon
1Department of Pathology MC 1089, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. g-getz@uchicago.edu
Current Opinion in Lipidology
|May 29, 2004
Summary
Paraoxonase 1 (PON1) protects against cardiovascular disease by reducing LDL oxidation and macrophage oxidative stress. Further research is needed to clarify PON1
Area of Science:
- Biochemistry
- Cardiovascular Science
- Genetics
Background:
- The paraoxonase (PON) family includes PON1, PON2, and PON3, sharing structural and enzymatic properties like hydrolyzing oxidized lipids in LDL.
- Despite conserved differences across species, the precise functions of individual PON family members remain unclear.
Purpose of the Study:
- To review the mechanisms of paraoxonase action and highlight differences between PON family members that require further investigation.
- To discuss the role of paraoxonases in cardiovascular disease, particularly atherosclerosis.
Main Methods:
- Review of existing literature on PON1, PON2, and PON3.
- Analysis of studies involving PON1 transgenic and knockout mice.
- Examination of human genetic polymorphism studies related to PON1.
Main Results:
- PON1 protects against atherosclerosis, likely via antioxidant effects on LDL and macrophages.
- PON1 association with HDL is complex and influenced by apolipoproteins and other factors.
- PON1 exhibits phospholipase A2 activity, impacting macrophage cholesterol biosynthesis.
- Increased oxidative stress in macrophages of PON1-deficient mice occurs despite PON2 and PON3 expression.
Conclusions:
- Plasma PON1 levels significantly impact cardiovascular disease risk due to its antioxidant properties.
- The exact mechanisms of PON1's cardioprotective effects on LDL and macrophages require further elucidation.
- The roles of PON2 and PON3 in atherosclerosis and their antioxidant functions warrant additional research.