Immunohistochemical Analysis of Paraoxonases and Chemokines in Arteries of Patients with Peripheral Artery Disease

Abstract

Oxidative damage to lipids and lipoproteins is implicated in the development of atherosclerotic vascular diseases, including peripheral artery disease (PAD). The paraoxonases (PON) are a group of antioxidant enzymes, termed PON1, PON2, and PON3 that protect lipoproteins and cells from peroxidation and, as such, may be involved in protection against the atherosclerosis process. PON1 inhibits the production of chemokine (C–C motif) ligand 2 (CCL2) in endothelial cells incubated with oxidized lipoproteins. PON1 and CCL2 are ubiquitously distributed in tissues, and this suggests a joint localization and combined systemic effect. The aim of the present study has been to analyze the quantitative immunohistochemical localization of PON1, PON3, CCL2 and CCL2 receptors in a series of patients with severe PAD. Portions of femoral and/or popliteal arteries from 66 patients with PAD were obtained during surgical procedures for infra-inguinal limb revascularization. We used eight normal arteries from donors as controls. PON1 and PON3, CCL2 and the chemokine-binding protein 2, and Duffy antigen/chemokine receptor, were increased in PAD patients. There were no significant changes in C–C chemokine receptor type 2. Our findings suggest that paraoxonases and chemokines play an important role in the development and progression of atherosclerosis in peripheral artery disease.

Attenuation of oxidative stress-induced lesions in skeletal muscle in a mouse model of obesity-independent hyperlipidaemia and atherosclerosis through the inhibition of Nox2 activity

“…Atherosclerosis and hyperlipidaemia may also exert effects on skeletal muscle [7,8]. For example, the effect of atherosclerosis and hyperlipidaemia on skeletal muscle morphology and function has been investigated in the context of peripheral arterial disease (PAD).…”

Plasma Energy-Balance Metabolites Discriminate Asymptomatic Patients with Peripheral Artery Disease

“…The emerging metabolomic approaches are providing new clues in understanding atherosclerosis-related cardiovascular disease [ 14 – 20 ], but efforts on PAD have been scarce. Previous studies from our group suggested that serum paraoxonase-1 (PON1) and the chemokine (C-C) motif ligand 2 (CCL2) might be useful biomarkers of PAD [ 21 , 22 ]: PON1 being a scavenger of excessive reactive oxygen species [ 23 ] and CCL2 an inducer of monocyte migration and differentiation into macrophages [ 24 ]. As mitochondrial dysfunction and inflammation result in disrupted metabolism [ 25 , 26 ], we report here that metabolomic profiling of plasma may be useful for identifying patients at increased risk of PAD and that energy-balance metabolites are associated with inflammation and oxidation in these patients.…”

Crossroads between peripheral atherosclerosis, western-type diet and skeletal muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral arterial disease

“…In fact, triglyceride accumulation in the adipose tissue leads to increased expression of pro-inflammatory cytokines and adipokines, such as resistin and visfatin that beyond promoting atherosclerosis, could potentially induce oxidative stress in skeletal muscle [147, 276–279]. Systemic low grade inflammation is evident in both Ldlr -/- and ApoE -/- experimental atherosclerotic mouse models with increased plasma concentrations of TNFα, IL1β and MCP1 [194].…”