Homocysteine, a non-
protein amino acid, important risk factor for
atherosclerosis and
thrombosis, causes dysfunction of vascular endothelial cells traduced in inadequate vasodilatation mechanism, is pro-inflammatory and induces endoplasmic reticulum stress. The more reactive conformation is the
homocysteine thiolactone (HcyT), product to the nonspecific action of
methionyl-tRNA synthetase, which is incorporated into
proteins by
disulfide bonds (S-homocysteinilation) or
amide bonds (N-homocysteinilation) affecting
protein structure and function leading to cell toxicity, autoimmune responses and
atherogenesis. The
enzyme paraoxonase-1 (PON1), part of
high density lipoprotein (HDL), had been studied only for its ability to hydrolyze
organophosphate derivatives. But, more recently it has been attributed other important role. The
enzyme activities are involving in protecting against the development of
atherosclerosis, by preventing oxidation of
lipoproteins and hydrolyze HcyT. There is growing evidence about the protective role of PON1 in
vascular disease. Genetic factors (polymorphisms of the PON1), environmental and lifestyle influence their concentration and
biological activity, but drugs used as cardioprotectives and
lipid-lowering or others, such as
antibiotics and
steroids, are also important modulators. This review is an updated of the most prominent information on clinical and experimental studies for understanding the role of the PON-1 in the protection against development of
atherosclerosis.