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

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.

Understanding the role of circulating chemokine (C-C motif) ligand 2 in patients with chronic ischemia threatening the lower extremities

“…22 We did not find significant difficulties in recalling past events and main exclusion criteria were acute ischemia, signs of infection, renal failure, liver disease, cancer, or autoimmune diseases. The number of patients recruited within our fixed term of 3 years (n=174) was higher than the minimal sample size required to analyze biological markers with this design, and taking into account the incidence and laboratory variability [6][7][8] (α=0.02, β=0.85; n=125). Diabetes, hypertension and dyslipidemia were defined according to established criteria.…”

“…However, these did not affect genetic studies and, presumably, did not skew the results of other comparisons. 7 …”

“…[1][2][3][4][5][6] Therefore, the search for laboratory surrogates is a relevant pursuit. We aimed to increase our understanding of the chemokine (C-C motif) ligand 2 (CCL2) in the overall inflammatory response observed in patients who develop chronic limb ischemia in order to identify associated factors [7][8][9][10][11][12] and to test the hypothesis that the expression of this chemokine and its receptors is increased in diseased arteries. This is based on our previous findings indicating that CCL2 and CCR2 (its cell surface receptor) are widely distributed in mice.…”

“…7,[14][15][16][17][18] We have already shown that serum CCL2 levels are consistently higher than plasma CCL2 levels and that analytical variability is significantly higher in serum. 18 This finding may alter the relevance of the observed clinical associations.…”

Monocyte chemoattractant protein-1 and paraoxonase-1 and 3 levels in patients with sepsis treated in an intensive care unit: a preliminary report

“…MCP-1 is central to the infl ammatory response as a mediator of monocyte recruitment into tissues and their subsequent differentiation into macrophages (12) . Several lines of evidence suggest that PON1 and MCP-1 coordinately regulate the infl ammatory response (8,13) . Clinical studies suggest that circulating MCP-1 concentration or serum PON1 lactonase and esterase activities, or both, may be biomarkers of a variety of diseases involving an infl ammatory response to an increased oxidative stress (14 -18) .…”