Plasma heme oxygenase-1 is decreased in peripheral artery disease patients

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. A number of emerging risk factors, including oxidative stress biomarkers, free radicals and heat shock proteins, may add to the established risk factors for cardiovascular disease (CVD). The present study assessed surrogate markers of oxidative stress, including total reduced glutathione (GSH), lipid hydroperoxides (LOOH), isoprostanes, heme oxygenase‑1 (HO‑1) and metabolic biomarkers, such as adiponectin and lactate, in PAD patients (n=27). Healthy age‑matched volunteers (n=27) served as controls. GSH and LOOH were evaluated by measuring total thiol groups and iron oxidation, respectively, by spectrophotometric analysis. Adiponectin, isoprostanes and HO‑1 levels were determined using commercially available ELISA kits and lactate level was determined colorimetrically. Results from patients with PAD demonstrated no significant difference in GSH content and LOOH formation when compared with healthy controls (5.1±7.6 vs. 6.9±9.1 nmol/ml and 6.8±14.2 vs. 8.3±14.9 nmol/ml, respectively), however, isoprostanes were demonstrated to be significantly reduced (3.8±4.8 pg/ml vs. 120±91 pg/mll; P<0.001). Furthermore, HO‑1, a protective heat shock protein, was significantly reduced in PAD patients (0.8±0.7 vs. 3.4±1.3 ng/ml; P<0.001). Adiponectin, an antiatherogenic adipokine, was not significantly different between the two groups (1.4±0.2 vs. 1.5±0.5 µg/ml), whereas serum lactate was significantly higher in PAD patients compared with controls (0.11±0.01 vs. 0.1±0.01 mM; P<0.05). Using multivariate analysis, HO‑1, hypertension, smoking and dyslipidemia were indicated to be independently associated with the presence of PAD, while only ankle‑brachial index was an independent predictor of severity of PAD. The oxidative pathway may be partially involved in the onset and progression of PAD and may represent a target to reduce the risk of ischemic events.