This study showed that altered HDL subclasses distribution, changed PON1 activities on different HDL subclasses as well as diminished anti-oxidative protection could be important factors in atherosclerosis development in CKD and ESRD patients.
Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies.
Our study suggests that serum paraoxonase (PON1) is not associated with cerebral hemorrhage or infarction, although it is a lipolactonase which is associated with HDL-apolipoprotein A-I (HDL-apoA-I) and plays a role in the prevention of atherosclerosis.
Paraoxonase-1 (PON1) is the antioxidant marker of high-density lipoproteins protecting against atherosclerosis and coronary artery disease (CAD) phenotype.
PON1 inhibits the oxidation of HDL and low density lipoprotein (LDL), and is involved in the pathogenesis of a variety of diseases including atherosclerosis.
Our findings thus raise the possibility that PON1 may be of importance in both the genetic and acquired predisposition to premature atherosclerosis and neuropathy in diabetes.
Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidation of low-density lipoprotein (LDL) in vitro, suggesting that PON1 protects against atherosclerosis.
Paraoxonase 1 is much the most extensively researched and strategies will hopefully emerge to increase its activity and provide a more satisfactory test of the antioxidant hypothesis of atherosclerosis than antioxidant vitamins have done.
The Q192R (rs662; A/G) polymorphism, which results in the glutamine to arginine substitution at position 192, of the PON1 gene has been linked to increased atherosclerosis risk in several but not all population studies.
Studies in the last 2 decades have demonstrated PON1's ability to protect against atherosclerosis by hydrolyzing specific derivatives of oxidized cholesterol and/or phospholipids in oxidized low-density lipoprotein and in atherosclerotic lesions.
We related the PON1M55L genotypes to the extent of atherosclerosis in left anterior descending coronary artery (LAD) in alcohol abstainers (0-1 g of alcohol/day), moderate consumers (1-36 g of alcohol/day) and drinkers (> 36 g of alcohol/day).
Homocysteine (Hcy)-thiolactonase (HTase) activity of the paraoxonase-1 (PON1) protein detoxifies Hcythiolactone in human blood and could thus delay the development of atherosclerosis.
The PON1 polymorphism and atherosclerosis would not appear to be associated with risk of CAA in the elderly, although further study with larger samples is necessary for confirmation.
<b>Background:</b> Paraoxonase 1 (PON1: EC 3.1.8.1) is a vital antioxidant enzyme against mainly atherosclerosis and many other diseases associated with oxidative stress.
Our data suggest a coordinated role between CCL2 and PON1 that may be detected in blood with simple measurements and may represent an indicator of the extent of atherosclerosis.
Understanding the mechanism that causes lower PON1 activity could provide the possibility for modulation of enzyme activity in purpose of preventing and/or decreasing development of atherosclerosis.
PON1 transgenic mice are at lower risk for atherosclerosis, which is consistent with PON1 gene knockout studies in mice and human genetic polymorphism studies.
The elevated activities of PON1 and HDL-PAF-AH could explain the increased resistance of PD-HDL to oxidation; the higher activity of total PAF-AH and the decreased HDL-PAF-AH/ total PAF-AH ratio could contribute to the increased incidence of atherosclerosis in these patients.
We conclude that, in addition to paraoxonase 1, both paraoxonase 2 and paraoxonase 3 proteins are protective against the development of atherosclerosis in mice.