Paraoxonases and cardiovascular diseases: pharmacological and nutritional influences

@article{Aviram2005ParaoxonasesAC,
  title={Paraoxonases and cardiovascular diseases: pharmacological and nutritional influences},
  author={Michael Aviram and Mira Rosenblat},
  journal={Current Opinion in Lipidology},
  year={2005},
  volume={16},
  pages={393–399}
}
Purpose of review To summarize the new articles published in the last year on paraoxonases, including their expression in cardiovascular diseases, and regulation by pharmacological and nutritional means. Recent findings The elucidation of the crystal structure of the paraoxonase 1 (PON1) gene, obtained by directed evolution, shows that it consists of a six-bladed β-propeller with a unique active site. PON1 is present in HDL but also in lipoprotein-deficient serum, in VLDL and in chylomicrons… 
Regulation of Hepatic Paraoxonase-1 Expression
TLDR
Recent progress in understanding the regulation of PON1 expression in hepatocytes is summarized, which shows that pharmacological modulation of Pon1 activity or P ON1 gene expression could constitute a useful approach for preventing atherosclerosis.
The human paraoxonase gene cluster as a target in the treatment of atherosclerosis.
TLDR
Evidence is provided that the PON cluster is a prospective target for the treatment of atherosclerosis and clinical observations focusing on gene polymorphisms indicate that PON1, PON2, and PON3 are protective against coronary artery disease.
Paraoxonase: Its antiatherogenic role in chronic renal failure
TLDR
Enhancement or maintenance of the PON1 activity may prevent development of CVDs and its consequences in patients on hemodialysis.
The human paraoxonase-1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters.
TLDR
The PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on Pon1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.
Paraoxonases function as unique protectors against cardiovascular diseases and diabetes: Updated experimental and clinical data
TLDR
Accumulating evidence from clinical research indicates that PON enzymes function as potential protectors in human cardiovascular diseases and related disorders, and this review describes the biochemical properties and molecular regulation of PON and summarizes the major recent findings on the functions of Pon.
Determinants of variation in human serum paraoxonase activity
TLDR
This study identified environmental and genetic determinants of PON1 activity that accounted for 88–97% of total phenotypic variance, suggesting that few, if any, major biological determinants are unrepresented in the models.
Dietary antioxidants and paraoxonases against LDL oxidation and atherosclerosis development.
TLDR
Recent data on the anti-atherosclerotic effects and mechanism of action of three major groups of dietary antioxidants-vitamin E, carotenoids and polyphenolic flavonoids are presented.
Biological role, protein expression, subcellular localization, and oxidative stress response of paraoxonase 2 in the intestine of humans and rats.
TLDR
The observations demonstrate that the human intestine is preferentially endowed with a marked PON2 expression compared with the rat intestine and this expression shows a developmental and intracellular pattern of distribution, and suggest Pon2 protective effects against prooxidant stimuli in the small intestine.
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References

SHOWING 1-10 OF 88 REFERENCES
Paraoxonase, a cardioprotective enzyme: continuing issues
TLDR
PON1 mass and activity in the plasma significantly influence the risk of developing cardiovascular disease and the role of PON2 and PON3 in atherosclerosis and their antioxidant properties with respect to LDL and macrophages also merit further investigation.
Pharmacogenetics of paraoxonases: a brief review
TLDR
A major goal in present research on the paraoxonases is to identify their natural substrates and to elucidate the mechanism(s) of their catalytic activities.
Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins.
TLDR
Transient and stable transfection assays in HuH7 cells indicated that the modulation of the mRNA and enzymatic activity levels could be accounted for by the regulation of the PON-1 gene promoter activity by these drugs.
Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes
TLDR
The first crystal structure of a PON family member, a variant of PON1 obtained by directed evolution, is described, a six-bladed β-propeller with a unique active site lid that is also involved in HDL binding.
Induction of the Paraoxonase-1 Gene Expression by Resveratrol
TLDR
Observations suggest that the PON-1 gene induction may be involved in the cardioprotective properties of resveratrol and highlight a ligand-dependent differential modulation of AhR-sensitive genes.
Paraoxonase 1 activity, concentration and genotype in cardiovascular disease
TLDR
It is believed that genetic epidemiological studies of the paraoxonase 1 polymorphisms in relation to coronary heart disease should no longer be undertaken unless they are very large and prospective in nature and more research should be undertaken to discover the biochemical mechanisms underlying the mode of action of paraox onase 1 and the factors which modulate its activity and/or concentration.
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