Paraoxonase-1 inhibits oxidised LDL-induced MCP-1 production by endothelial cells

The upregulation of endothelial cell MCP-1 production by ox-LDL is a major initiating event in atherogenesis. HDL and PON1 retard the oxidation of LDL and therefore may retard endothelial cell MCP-1 production. The endothelial cell line EAhy926 was incubated with ox-LDL in the presence and absence of HDL and PON1 and the production of MCP-1 was measured by ELISA. Human HDL and PON1 significantly inhibited the in vitro oxidation of LDL and completely prevented the ox-LDL induced increase in MCP-1 production by endothelial cells. Ostrich HDL that does not contain PON1 was unable to prevent LDL-oxidation or the production of MCP-1 by endothelial cells. PON1 attenuates the ox-LDL induced MCP-1 production by endothelial cells. This is one, early, mechanism by which PON1 may be anti-atherogenic. © 2004 Elsevier Inc. All rights reserved

Serum paraoxonase and arylesterase activities of paraoxonase-1 (PON-1), mild cognitive impairment, and 2-year conversion to dementia: A pilot study

Converging lines of evidence suggest that paraoxonase-1 (PON-1) may confer protection against inflammatory and oxidative challenge which, in turn, plays a key-role in the onset and progression of dementia. The aim of this study was to evaluate whether serum PON-1 paraoxonase/arylesterase activities might predict the clinical conversion of mild cognitive impairment (MCI) to late-onset Alzheimer's disease (LOAD) or vascular dementia (VAD). Serum paraoxonase and arylesterase activities were measured by spectrophotometric assays at baseline in 141 MCI patients (median age: 77 years; interquartile range 71-81) and in 78 healthy controls (median age: 76 years; interquartile range 73-79). After 2 years of follow-up, 86 MCI remained stable (MCI/MCI), 34 converted to LOAD (MCI/LOAD), whereas 21 converted to VAD (MCI/VAD). Baseline arylesterase activity was lower in all MCI groups compared with controls (all p < 0.01), whereas paraoxonase activity was lower in MCI/VAD group compared to controls (p < 0.05) and MCI/MCI patients (p = 0.009). Low paraoxonase and arylesterase activities (I quartile) were associated to higher risk of conversion to VAD (OR: 3.74, 95% CI: 1.37-10.25 and OR: 3.16, 95% CI: 1.17-8.56, respectively). Our results suggest that in MCI patients low PON-1 activity might contribute to identify individuals susceptible to develop vascular dementia. Our study showed that in patients with mild cognitive impairment (MCI) low serum levels of paraoxonase-1 (PON-1) activity is associated with a higher likelihood of developing Vascular Dementia, but not Alzheimer's Disease. The observed connection might be explained by the ability of PON-1 to retard low-density lipoprotein (LDL) oxidation, decrease oxidative stress, attenuate inflammation, and increase cholesterol efflux