Novel links among peroxiredoxins, endothelial dysfunction, and severity of atherosclerosis in type 2 diabetic patients with peripheral atherosclerotic disease

Abstract

Peroxiredoxins, a group of antioxidant protein enzymes (PRDX1 to 6), are reported as antiatherogenic factors in animals; however, human studies are lacking. The present work aims to provide baseline data regarding the phenotype of PRDX1, 2, 4, and 6 in diabetic patients with peripheral atherosclerosis disease (PAD) and their relation to endothelial dysfunction (ED) and disease severity. Plasma levels of PRDX1, 2, 4, and 6 and markers of endothelial dysfunction (ICAM-1 and VCAM-1) were measured using ELISA in 55 type 2 diabetic patients having PAD and 25 healthy subjects. Anklebrachial index (ABI), body mass index (BMI), triglycerides (TG), total cholesterol, HbA1c, and insulin resistance (HOMA IR) were measured. PRDX1, 2, 4, and 6 levels were significantly higher in patients compared to controls (PRDX1 21.9±5.71 vs 16.8±3.9 ng/ml, P<0.001, PRDX2 36.5±14.83 vs 20.4±8.61 ng/ml, P<0.001, PRDX4 3,840±1,440 vs 2,696±1,972 pg/ml, P<0.005, PRDX6 311±110 vs 287.9±-114 pg/ml, P<0.05). PRDX1 and PRDX4 correlated negatively with ABI (r=−0.273, P<0.05 and r=−0.28, P<0.05, respectively), while PRDX1 and PRDX2 correlated positively with HOMA/IR and TG (r=0.276, P<0.01 and r=0.295, P<0.01, respectively). ICAM-1 was associated with PRDX2 and log PRDX6 (r=0.345, P=0.0037 and r=0.344, P=0.0038). Our results provide strong links among PRDXs, ED, and severity of PAD in diabetic patients which warrants further evaluation to clarify whether high circulating levels of PRDXs are a consequence of chronic atherosclerotic disease or a predisposing factor for later cardiovascular events.

Peroxiredoxin 6, a Novel Player in the Pathogenesis of Diabetes

“…Thus, PRDX6 may represent a specific target for antioxidant-based pharmacological interventions; moreover, PRDX6 oxidation level, for instance in blood cells, may represent a novel marker for monitoring oxidative/metabolic status and response to preventive therapy. In line with these ideas, PRDX6 levels were significantly higher in diabetic patients with endothelial dysfunction compared with control subjects, which may possibly represent a physiological adaptation against oxidative stress in patients with atherosclerosis (44). Moreover, another study (45) conducted in diabetic patients demonstrated that physical training was able to increase PRDXs levels measured in erythrocytes, counteracting the oxidative damage that is typical of diabetes.…”

Increased peroxiredoxin 4 levels in patients with prediabetes compared to normal glucose tolerance subjects

“…This increase in peroxiredoxins levels was associated with endothelial dysfunction, severity of peripheral arterial disease and comorbidities as triglycerides and insulin resistance. 24 There is, however, no data about peroxiredoxin levels in prediabetic conditions.…”

Close teamwork between Nrf2 and peroxiredoxins 1 and 6 for the regulation of prostaglandin D2 and E2 production in macrophages in acute inflammation

“…Prxs 1, 2, 4, and 6 can be secreted from cells and are present in plasma in healthy human, with Prx1 and Prx2 levels around 20 ng/ml, and Prx6 level around 0.3 ng/ml [26]. Prx1 is also detected in mouse body fluids, and the secretion of Prx1 from cultured cells was enhanced following the treatment with cytokines such as TGF-β, oncostatin M and IL1-β (reviewed in [27]).…”