[From organophosphate compound toxicity to atherosclerosis: role of paraoxonase 1].
OBJECTIVE
Paraoxonase 1 is an ubiquitous human serum and tissue esterase known to hydrolyse organophosphorous compounds. It seems to be implicated in various vascular diseases.


BACKGROUND
Recently paraoxonase has been located on the surface of High Density Lipoproteins (HDL) which has directed studies towards its involvement in atherosclerosis. An antioxidant effect has been suggested from its structure rich in reducing amino acids (cysteine), which was confirmed on low density lipoproteins (LDL) first in vitro and then in vivo. Paraoxonase 1 hydrolyses an arachidonic acid derivative found on the surface of oxidised LDL known to participate in the essential initial step of atherogenesis. Clinically paraoxonase 1 activity is low when pathological vascular ageing occurs early (myocardial infarction) and when cardiovascular risk is high (diabetes mellitus, chronic renal failure, analphalipoproteinemia).


CONCLUSIONS
The genetic polymorphism of this enzyme is one of the determinants of serum paraoxonase 1 activity variations. It could explain sensitivity differences in chronic organophosphate intoxications and has been suspected as a risk factor of vascular injury. A decrease of this enzyme activity with ageing could play a part in the high prevalence of cardiovascular diseases in the aged.
Dantoine
T
T
Département de gérontologie clinique, CHU de Limoges, 2, avenue Martin-Luther-King, 87042, Limoges, France. tdantoine@wanadoo.fr <tdantoine@wanadoo.fr>
Debord
J
J
Merle
L
L
Charmes
J-P
JP
D001161:Arteriosclerosis / Q000503:physiopathology*; D043303:Aryldialkylphosphatase; D008076:Cholesterol, HDL; D004950:Esterases / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D009943:Organophosphorus Compounds; D011110:Polymorphism, Genetic; D012307:Risk Factors
D008076:Cholesterol, HDL; D007306:Insecticides; D009943:Organophosphorus Compounds; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human