Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease

Background: Similar to remote ischemic preconditioning bouts of exercise may possess immediate protective effects against ischemia-reperfusion injury. However, underlying mechanisms are largely unknown. This study compared the impact of single and repeated handgrip exercise versus remote ischemic pr...

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Main Authors: Thijs R. J. Landman, Laween Uthman, Inge A. H. Hofmans, Yvonne Schoon, Frank-Erik de Leeuw, Dick H. J. Thijssen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2022.1026711/full
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author Thijs R. J. Landman
Laween Uthman
Inge A. H. Hofmans
Yvonne Schoon
Frank-Erik de Leeuw
Dick H. J. Thijssen
author_facet Thijs R. J. Landman
Laween Uthman
Inge A. H. Hofmans
Yvonne Schoon
Frank-Erik de Leeuw
Dick H. J. Thijssen
author_sort Thijs R. J. Landman
collection DOAJ
description Background: Similar to remote ischemic preconditioning bouts of exercise may possess immediate protective effects against ischemia-reperfusion injury. However, underlying mechanisms are largely unknown. This study compared the impact of single and repeated handgrip exercise versus remote ischemic preconditioning on inflammatory biomarkers in patients with cerebral small vessel disease (cSVD).Methods: In this crossover study, 14 patients with cSVD were included. All participants performed 4-day of handgrip exercise (4x5-minutes at 30% of maximal handgrip strength) and remote ischemic preconditioning (rIPC; 4x5-minutes cuff occlusion around the upper arm) twice daily. Patients were randomized to start with either handgrip exercise or rIPC and the two interventions were separated by > 9 days. Venous blood was drawn before and after one intervention, and after 4-day of repeated exposure. We performed a targeted proteomics on inflammation markers in all blood samples.Results: Targeted proteomics revealed significant changes in 9 out of 92 inflammatory proteins, with four proteins demonstrating comparable time-dependent effects between handgrip and rIPC. After adjustment for multiple testing we found significant decreases in FMS-related tyrosine kinase-3 ligand (Flt3L; 16.2% reduction; adjusted p-value: 0.029) and fibroblast growth factor-21 (FGF-21; 32.8% reduction adjusted p-value: 0.029) after single exposure. This effect did not differ between handgrip and rIPC. The decline in Flt3L after repeated handgrip and rIPC remained significant (adjusted p-value = 0.029), with no difference between rIPC and handgrip (adjusted p-value = 0.98).Conclusion: Single handgrip exercise and rIPC immediately attenuated plasma Flt3L and FGF-21, with the reduction of Flt3L remaining present after 4-day of repeated intervention, in people with cSVD. This suggests that single and repeated handgrip exercise and rIPC decrease comparable inflammatory biomarkers, which suggests activation of shared (anti-)inflammatory pathways following both stimuli. Additional studies will be needed to exclude the possibility that this activation is merely a time effect.
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spelling doaj.art-c4022e5a58d9479fa239f1b2d6edbe822022-12-22T02:46:35ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-11-011310.3389/fphys.2022.10267111026711Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel diseaseThijs R. J. Landman0Laween Uthman1Inge A. H. Hofmans2Yvonne Schoon3Frank-Erik de Leeuw4Dick H. J. Thijssen5Departmenet of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Centre, Gelderland, NetherlandsDepartmenet of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Centre, Gelderland, NetherlandsDepartmenet of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Centre, Gelderland, NetherlandsDepartmenet of Geriatric Medicine, Radboud Institute for Health Sciences, Radboud University Medical Centre, Gelderland, NetherlandsCenter for Cognitive Neuroscience, Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Gelderland, NetherlandsDepartmenet of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Centre, Gelderland, NetherlandsBackground: Similar to remote ischemic preconditioning bouts of exercise may possess immediate protective effects against ischemia-reperfusion injury. However, underlying mechanisms are largely unknown. This study compared the impact of single and repeated handgrip exercise versus remote ischemic preconditioning on inflammatory biomarkers in patients with cerebral small vessel disease (cSVD).Methods: In this crossover study, 14 patients with cSVD were included. All participants performed 4-day of handgrip exercise (4x5-minutes at 30% of maximal handgrip strength) and remote ischemic preconditioning (rIPC; 4x5-minutes cuff occlusion around the upper arm) twice daily. Patients were randomized to start with either handgrip exercise or rIPC and the two interventions were separated by > 9 days. Venous blood was drawn before and after one intervention, and after 4-day of repeated exposure. We performed a targeted proteomics on inflammation markers in all blood samples.Results: Targeted proteomics revealed significant changes in 9 out of 92 inflammatory proteins, with four proteins demonstrating comparable time-dependent effects between handgrip and rIPC. After adjustment for multiple testing we found significant decreases in FMS-related tyrosine kinase-3 ligand (Flt3L; 16.2% reduction; adjusted p-value: 0.029) and fibroblast growth factor-21 (FGF-21; 32.8% reduction adjusted p-value: 0.029) after single exposure. This effect did not differ between handgrip and rIPC. The decline in Flt3L after repeated handgrip and rIPC remained significant (adjusted p-value = 0.029), with no difference between rIPC and handgrip (adjusted p-value = 0.98).Conclusion: Single handgrip exercise and rIPC immediately attenuated plasma Flt3L and FGF-21, with the reduction of Flt3L remaining present after 4-day of repeated intervention, in people with cSVD. This suggests that single and repeated handgrip exercise and rIPC decrease comparable inflammatory biomarkers, which suggests activation of shared (anti-)inflammatory pathways following both stimuli. Additional studies will be needed to exclude the possibility that this activation is merely a time effect.https://www.frontiersin.org/articles/10.3389/fphys.2022.1026711/fullexerciseremote ischemic preconditioningcerebral small vessel diseaseinflammationproteomics
spellingShingle Thijs R. J. Landman
Laween Uthman
Inge A. H. Hofmans
Yvonne Schoon
Frank-Erik de Leeuw
Dick H. J. Thijssen
Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease
Frontiers in Physiology
exercise
remote ischemic preconditioning
cerebral small vessel disease
inflammation
proteomics
title Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease
title_full Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease
title_fullStr Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease
title_full_unstemmed Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease
title_short Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease
title_sort attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease
topic exercise
remote ischemic preconditioning
cerebral small vessel disease
inflammation
proteomics
url https://www.frontiersin.org/articles/10.3389/fphys.2022.1026711/full
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