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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.
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http://dx.doi.org/10.5551/jat.42432 | DOI Listing |
Front Surg
December 2024
Department of General, Visceral, Vascular and Transplant Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Background: Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease (PAD). Patients with diabetes mellitus (DM) have a faster progression of PAD and a fourfold increased risk of CLTI compared to patients without DM. Epidural spinal cord stimulation (SCS) has been used as a method to improve microcirculation, relieve ischemic pain and reduce the number of amputations in patients with PAD.
View Article and Find Full Text PDFEur J Clin Pharmacol
December 2024
Health Management and Economics Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran.
Purpose: This study aimed to systematically review the cost-effectiveness of rivaroxaban plus aspirin (RIV + ASA) versus aspirin (ASA) alone in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD).
Methods: A systematic review was conducted using leading databases including PubMed, Scopus, and Web of Science core collection. The search was carried out up to June 25, 2024, focusing on identifying full economic evaluation studies comparing the cost-effectiveness of RIV + ASA versus ASA alone in patients with stable cardiovascular diseases (CVDs).
Gut Microbes
December 2025
Institut National de la Santé et de la Recherche Médicale (INSERM), InCOMM Intestine ClinicOralOmics Metabolism & Microbiota UMR1297 Inserm / Université Toulouse III, Toulouse, France.
Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures.
View Article and Find Full Text PDFRegional neuron loss following stroke can result in remote brain changes due to diaschisis and secondary brain atrophy. Whole brain changes post-stroke can be captured by the predicted brain age difference (brain-PAD), a neuroimaging-derived biomarker of global brain health previously associated with poorer chronic stroke outcomes. We hypothesized that greater lesion damage would be longitudinally associated with worsening brain-PAD during subacute stroke, and conversely, that poorer baseline brain-PAD would be associated with enlarged lesion damage.
View Article and Find Full Text PDFVasc Med
December 2024
Vascular & Interventional Specialists of Orange County, Orange, CA, USA.
Background: Preclinical studies have demonstrated that therapeutic ultrasound (TUS) increases perfusion in peripheral artery disease (PAD). This pilot study assessed the safety and effectiveness of a noninvasive TUS device in patients with advanced PAD.
Methods: A phased array of TUS transducers was fabricated on a wearable sleeve, designed to sonicate the posterior and anterior tibial arteries (and their collaterals) at the calf level.
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