Paraoxonase-1 activity modulates endothelial function in patients with peripheral arterial disease.

Human serum paraoxonase-1 (PON1) is thought to play a role in the favorable vascular effects of high-density lipoproteins, mainly through a reduction in low-density lipoprotein oxidation. Endothelial dysfunction, characterized by an impaired capacity of the arteries to dilate in response to a number of stimuli, represents the earliest stage of atherosclerosis. We performed the present study in 37 patients with peripheral arterial disease, with the aim of investigating the influence of PON1 Q192R polymorphism and activity on peripheral endothelial function, evaluated as brachial-artery flow-mediated vasodilation (FMV). Patients with the R allele (QR or RR genotype, n=19) had significantly higher PON1 activity [408 U/mL (309-456) versus 180 U/mL (141-243), p<0.001] and greater brachial FMV (5.7+/-3.9% versus 3.0+/-2.8%, p<0.001) than those with Q allele (QQ genotype, n=18). In the whole population, PON1 activity showed a direct relation to brachial FMV (r=0.46, p=0.004). In a multivariate linear regression analysis, the only independent predictors of brachial FMV were PON1 activity (beta=0.40, p=0.008), brachial-artery diameter (beta=-0.39, p=0.01) and male sex (beta=-0.27, p=0.04). These finding support the importance of PON1 activity as a modulating factor of the endothelial function.