AIM: Ischemia-reperfusion (I-R) produces reactive oxygen species (ROS) that damage cells and favour cytotoxicity and apoptosis in peripheral artery disease (PAD) patients. Since brief episodes of I-R (ischemic conditioning) protect cells against ischemic harms, we evaluated whether a short-course of supervised treadmill training, characterized by repeated episodes of I-R, makes peripheral blood mononuclear cells (PBMCs) from PAD patients with intermittent claudication more resistant to I-R injuries by reducing oxidative stress and by inducing an adaptative response of unfolded protein response (UPR) and nuclear factor-E2-related factor (Nrf2) pathway expression. METHODS: 24 PAD patients underwent 21 sessions of treadmill training and a treadmill test as indicator of acute response to I-R. RESULTS: Maximal and pain free walking distance improved (p<0.01), whereas LDH leakage and apoptosis of PBMCS decreased (p<0.01); plasma malondialdehyde and ROS generation in PBMCS declined, while plasma glutathione augmented (p<0.01). Moreover we demonstrated an up-regulation of UPR and Nrf2 expression in PBMCS (p<0.01). To understand whether treadmill training may act as a trigger of ischemic conditioning, we examined the effect of repeated episodes of I-R on adaptative response in PBMCS derived from the patients. We showed an up-regulation of UPR and Nrf2 gene expression (p<0.01), while oxidative stress and cytotoxicity, after an initial increase, declined (p<0.01). This positive effect on cytotoxicity was reduced after inhibition of UPR and Nrf2 pathways. CONCLUSIONS: Treadmill training in PAD patients through UPR and Nrf2 up-regulation may trigger hypoxic adaptation similar to conditioning, thus modifying cell survival.

Physical Exercise Reduces Cytotoxicity and Up-Regulates Nrf2 and UPR Expression in Circulating Cells of Peripheral Artery Disease Patients: An Hypoxic Adaptation?

Fratta Pasini AM;De Marchi S
Membro del Collaboration Group
;
2018-01-01

Abstract

AIM: Ischemia-reperfusion (I-R) produces reactive oxygen species (ROS) that damage cells and favour cytotoxicity and apoptosis in peripheral artery disease (PAD) patients. Since brief episodes of I-R (ischemic conditioning) protect cells against ischemic harms, we evaluated whether a short-course of supervised treadmill training, characterized by repeated episodes of I-R, makes peripheral blood mononuclear cells (PBMCs) from PAD patients with intermittent claudication more resistant to I-R injuries by reducing oxidative stress and by inducing an adaptative response of unfolded protein response (UPR) and nuclear factor-E2-related factor (Nrf2) pathway expression. METHODS: 24 PAD patients underwent 21 sessions of treadmill training and a treadmill test as indicator of acute response to I-R. RESULTS: Maximal and pain free walking distance improved (p<0.01), whereas LDH leakage and apoptosis of PBMCS decreased (p<0.01); plasma malondialdehyde and ROS generation in PBMCS declined, while plasma glutathione augmented (p<0.01). Moreover we demonstrated an up-regulation of UPR and Nrf2 expression in PBMCS (p<0.01). To understand whether treadmill training may act as a trigger of ischemic conditioning, we examined the effect of repeated episodes of I-R on adaptative response in PBMCS derived from the patients. We showed an up-regulation of UPR and Nrf2 gene expression (p<0.01), while oxidative stress and cytotoxicity, after an initial increase, declined (p<0.01). This positive effect on cytotoxicity was reduced after inhibition of UPR and Nrf2 pathways. CONCLUSIONS: Treadmill training in PAD patients through UPR and Nrf2 up-regulation may trigger hypoxic adaptation similar to conditioning, thus modifying cell survival.
2018
Nrf2
UPR
PAD
Oxidative stress
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/981038
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