SUPERVISED INTENSIVE TRAINING IMPROVES OXIDATIVE DEFENSIVE PATHWAYS AND REDUCES INFLAMMATION IN PERIPHERAL ARTERY DISEASE

Background: recent evidences suggest that exercise training may ameliorate oxidative stress in patients with peripheral arterial disease (PAD) and reduce inflammation. Few data are available on mechanisms involved. Nuclear related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response ; Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury. Also monocytes (CD16+) are recognizesd as an important actor in aterosclerosis. Aim: to evaluate in PAD the effects of controlled exercise training on oxidative stress, Nrf2 gene expression and monocyte subsets. Methods: 24 patients, with PAD at Fontaine stage II, underwent a 3-weeks (5 days per week) period of supervised training with treadmill walking conducted until pain onset with subsequent rest and walking again for total 40 minutes of exercise. At beginning (D0) and at the end of the program (D21) were evaluated: pain-free walking time (PFWT), maximal walking time (MWT), monocyte subsets by flow cytometry, malondialdehyde (MDA), as marker of oxidative stress, total RNA (extracted from PBMCs to evaluate Nrf2 expression by RT-PCR). Results: the 3-week training significantly increased PWFT and MWT (p=0.001); plasma levels of MDA decreased (p=0.002), levels of mRNA Nrf2 increased after the exercise program (p=0.004, figure 1 ); finally, the percentage of inflammatory monocytes decreased, and conversely classical monocytes increased (figure 2). Conclusions: Our study shows that training in PAD patients improves walking time, furthermore it reduces oxidative stress (decrease of MDA) and increases anti-oxidative defensive system enhancing Nrf2-gene expression. The training elicited multiple episodes of ischemia-reperfusion every day and, since Nrf2 is involved in protecting from ischemia-reperfusion injury we can infer that somehow we "trained" also Nrf2 system. The shift of monocytes subtype from an inflammatory to a classic subtype suggests a deep change in inflammation profile of these patients with training.