The Role of Combined Assessment of Defense Against Oxidative Stress and Inflammation in the Evaluation of Peripheral Arterial Disease

A.      Rull; R.      Garcia; L.      Fernandez-Sender; R.      Beltran-Debon; G.      Aragones; J.      M. Alegret; C.      Alonso-Villaverde; B.      Mackness; M.      Mackness; J.      Camps; V.      Martin-Paredero; J.      Joven

doi:10.2174/156652411796268713

Abstract

Atherosclerosis in symptomatic peripheral arterial disease affects wide portions of numerous arteries in lower extremities. The resulting active inflammation in a considerable amount of arterial tissue facilitates systemic detection via measurement of inflammation-related variables. We reasoned that the combined assessment of defense against oxidative stress, in the form of paraoxonase-1 (PON1), and monocyte migration measured as circulating (C-C motif) ligand 2 (CCL2), may play a role in the evaluation of these patients. Plasma CCL2 and serum PON1-related variables, assessed by their interaction with functional genetic variants, were measured in a cross-sectional study in patients with symptomatic PAD. We found that PON1 activity and concentration were significantly lower and CCL2 concentration higher in PAD patients compared to controls, that the combination of plasma CCL2 and PON1- related values, especially PON1 concentration differentiated, almost perfectly, controls from patients and that the expression of CCL2 and PON1 generally co-localized in the atherosclerotic lesion. Since no association with genetic variants was found, such a relationship is probably the result of the disease. Our data suggest a coordinated role between CCL2 and PON1 that may be detected in blood with simple measurements and may represent an indicator of the extent of atherosclerosis.

Keywords: Atherosclerosis, CCL2, inflammation, lactonase, monocyte chemoattractant protein-1, paraoxonase-1, peripheral vascular disease, polymorphism, peripheral arterial disease, Plasma, serum, disease, Cytokines, biomarkers, oxidative stress