Galectin-3 is a modulator of oxidative stress, inflammation, and fibrogenesis involved in the pathogenesis of vascular diseases. The present study sought to characterize, in patients with peripheral artery disease (PAD), the localization of galectin-3 in arterial tissue, and to analyze the relationships between the circulating levels of galectin-3 and oxidative stress and inflammation. It also sought to compare the diagnostic accuracy of galectin-3 with that of other biochemical markers of this disease. We analyzed femoral or popliteal arteries from 50 PAD patients, and four control arteries. Plasma from 86 patients was compared with that from 72 control subjects. We observed differences in the expression of galectin-3 in normal arteries, and arteries from patients with PAD, with a displacement of the expression from the adventitia to the media, and the intima. In addition, plasma galectin-3 concentration was increased in PAD patients, and correlated with serologic markers of oxidative stress (F2-isoprostanes), and inflammation [chemokine (C−C motif) ligand 2, C-reactive protein, β-2-microglobulin]. We conclude that the determination of galectin-3 has good diagnostic accuracy in the assessment of PAD and compares well with other analytical parameters currently in use.

We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated with endothelial cells. HUVEC cells were incubated with native LDL, oxidized LDL, oxidized LDL plus HDL from wild type mice, and oxidized LDL plus HDL from PON1-deficient mice. Results showed alterations in carbohydrate and phospholipid metabolism and increased apoptosis in cells incubated with oxidized LDL. These changes were partially prevented by wild type mouse HDL, but the effects were less effective with HDL from PON1-deficient mice. Our results suggest that PON1 may play a significant role in endothelial cell survival by protecting cells from alterations in the respiratory chain induced by oxidized LDL. These results extend current knowledge on the protective role of HDL and PON1 against oxidation and apoptosis in endothelial cells.

Oxidative stress (OS) resulting from an imbalance between reactive oxygen species (ROS) generation and antioxidant defenses plays a pivotal role in vascular diseases such as atherosclerosis and hypertension. ROS derived from NADPH oxidase, mitochondria, and xanthine oxidase promote endothelial dysfunction by inducing lipid and protein oxidation, apoptosis, and pro-inflammatory signaling, thereby enhancing smooth muscle proliferation and atherogenesis. This review summarizes the molecular mechanisms linking OS to vascular injury and aims to systematically elucidate the role of OS in vascular diseases, with a specific focus on critiquing the current challenges in translating biomarkers to clinical practice and the emerging trends in personalized antioxidant therapy. Particular attention is given to biomarkers of oxidative stress, including those assessing antioxidant enzyme activity and oxidative damage products, which possess potential for clinical use. Therapeutic strategies targeting OS, including dietary and pharmacological antioxidants, show promise in improving vascular health, although clinical outcomes have been inconsistent and it is necessary to resolve the standardization and validation of these biomarkers, develop precise targeted therapies against specific ROS sources (e.g., NOX inhibitors, mitochondrial antioxidants), and explore personalized clinical trials based on redox stratification. Overall, OS is a central mediator in vascular pathology, and progress in biomarker validation and targeted therapies will be essential to translate current knowledge into effective prevention, diagnosis, and treatment of cardiovascular diseases. Personalized approaches based on accurate redox profiling may enhance efficacy.

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.