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-density lipoprotein (LDL) by hydrolysing LDL-associated phospholipid and cholesteryl-ester hydroperoxides. We have examined the relationship between PON1 and atherosclerosis development in transgenic rabbits overexpressing human apolipoprotein (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) while high-density lipoprotein (HDL) cholesterol was 1.84 +/- 0.54 mmol/L in transgenic rabbits and 0.57 +/- 0.21 mmol/L in control rabbits (P = 0.0001). After feeding rabbits a high-cholesterol diet for 14 weeks HDL-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 compared to week 0). The amount of thoracic aortic surface area covered by lesions was 29 +/- 16% in the control group and 26 +/- 15% in the transgenic group (P = NS). A pro-atherosclerotic diet reduces PON1 which may exaggerate the effects of the diet on the development of atherosclerosis.
Mackness
M
M
Department of Medicine, University of Manchester, Manchester, United Kingdom. mmack@central.cmht.nwest.nhs.uk
Boullier
A
A
Hennuyer
N
N
Mackness
B
B
Hall
M
M
Tailleux
A
A
Duriez
P
P
Delfly
B
B
Durrington
P
P
Fruchart
J C
JC
Duverger
N
N
Caillaud
J M
JM
Castro
G
G
Bouiller
A
A
D000818:Animals; D030801:Animals, Genetically Modified; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D001161:Arteriosclerosis / Q000201:enzymology* / Q000209:etiology*; D043303:Aryldialkylphosphatase; D008076:Cholesterol, HDL / Q000097:blood; D004036:Diet, Atherogenic; D004950:Esterases / Q000097:blood*; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D010084:Oxidation-Reduction; D011817:Rabbits
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human