Paraoxonase activity is reduced by a pro-atherosclerotic diet in rabbits

Serum paraoxonase (PON1) is believed to protect against the development of atherosclerosis because of its ability to retard the oxidation of low-densi ty lipoprotein (LDL) by hydrolysing LDL-associated phospholipid and cholest eryl-ester hydroperoxides. We have examined the relationship between PON1 a nd atherosclerosis development in transgenic rabbits overexpressing human a polipoprotein (apo) A-I and nontransgenic littermates fed a pro-atherogenic diet. PON1 activity was higher in transgenic (4006.1 +/- 716.7 nmol/min/ml ) compared to control (3078.5 +/- 623.3 nmol/min/ml) rabbits (P < 0.01) whi le high-density lipoprotein (HDL) cholesterol was 1.84 +/- 0.54 mmol/L in t ransgenic rabbits and 0.57 +/- 0.21 mmol/L in control rabbits (P = 0.0001). After feeding rabbits a high-cholesterol diet for 14 weeks RDL-cholesterol fell by 70% in both transgenic and control rabbits (P < 0.001 compared to week 0) PON1 activity fell by 50% in both groups of rabbits (P < 0.01 compa red to week 0). The amount of thoracic aortic surface area covered by lesio ns was 29 +/- 16% in the control group and 26 +/- 15% in the transgenic gro up (P = NS). A pro-atherosclerotic diet reduces PON1 which may exaggerate t he effects of the diet on the development of atherosclerosis. (C) 2000 Acad emic Press.