The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance

Tingting Gu; Jesper Just; Katrine Tang Stenz; Yan Yan; Peter Sieljacks; Jakob Wang; Thomas Skjaerlund Groennebaek; Jesper Emil Jakobsgaard; Emil Rindom; Jon Herskind; Anders Gravholt; Thomas Ravn Lassen; Mathias Jørgensen; Rikke Bæk; Eugenio Gutiérrez-Jiménez; Nina Kerting Iversen; Peter Mondrup Rasmussen; Jens Randel Nyengaard; Malene Møller Jørgensen; Frank de Paoli; Hans Erik Bøtker; Jørgen Kjems; Kristian Vissing; Kim Ryun Drasbek

doi:10.3390/ijms23063334

The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance

Tingting Gu, Jesper Just, Katrine Tang Stenz, Yan Yan, Peter Sieljacks, Jakob Wang, Thomas Skjaerlund Groennebaek, Jesper Emil Jakobsgaard, Emil Rindom, Jon Herskind, Anders Gravholt, Thomas Ravn Lassen, Mathias Jørgensen, Rikke Bæk, Eugenio Gutiérrez-Jiménez, Nina Kerting Iversen, Peter Mondrup Rasmussen, Jens Randel Nyengaard, Malene Møller Jørgensen, Frank de PaoliHans Erik Bøtker, Jørgen Kjems, Kristian Vissing, Kim Ryun Drasbek

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

13 Citations (Scopus)

Abstract

Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification.

Original language	English
Article number	3334
Journal	International Journal of Molecular Sciences
Volume	23
Issue	6
Number of pages	27
ISSN	1661-6596
DOIs	https://doi.org/10.3390/ijms23063334
Publication status	Published - Mar 2022

Keywords

Angiogenesis
Brain ischemia
Cell viability
Human brain vascular endothelial cells
Infarction
Plasma extracellular vesicles
Remote ischemic conditioning
Resistance exercise
Stroke
MOUSE-BRAIN
human brain vascular endothelial cells
INJURY
infarction
remote ischemic conditioning
plasma extracellular vesicles
CEREBRAL-ISCHEMIA
brain ischemia
MECHANISM
angiogenesis
PREVENTION
BLOOD-FLOW
stroke
HEART
cell viability
MODELS
EXOSOMES
resistance exercise
CELL

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Gu, T., Just, J., Stenz, K. T., Yan, Y., Sieljacks, P., Wang, J., Groennebaek, T. S., Jakobsgaard, J. E., Rindom, E., Herskind, J., Gravholt, A., Lassen, T. R., Jørgensen, M., Bæk, R., Gutiérrez-Jiménez, E., Iversen, N. K., Rasmussen, P. M., Nyengaard, J. R., Jørgensen, M. M., ... Drasbek, K. R. (2022). The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance. International Journal of Molecular Sciences , 23(6), Article 3334. https://doi.org/10.3390/ijms23063334

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title = "The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance",

abstract = "Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification.",

keywords = "Angiogenesis, Brain ischemia, Cell viability, Human brain vascular endothelial cells, Infarction, Plasma extracellular vesicles, Remote ischemic conditioning, Resistance exercise, Stroke, MOUSE-BRAIN, human brain vascular endothelial cells, INJURY, infarction, remote ischemic conditioning, plasma extracellular vesicles, CEREBRAL-ISCHEMIA, brain ischemia, MECHANISM, angiogenesis, PREVENTION, BLOOD-FLOW, stroke, HEART, cell viability, MODELS, EXOSOMES, resistance exercise, CELL",

author = "Tingting Gu and Jesper Just and Stenz, {Katrine Tang} and Yan Yan and Peter Sieljacks and Jakob Wang and Groennebaek, {Thomas Skjaerlund} and Jakobsgaard, {Jesper Emil} and Emil Rindom and Jon Herskind and Anders Gravholt and Lassen, {Thomas Ravn} and Mathias J{\o}rgensen and Rikke B{\ae}k and Eugenio Guti{\'e}rrez-Jim{\'e}nez and Iversen, {Nina Kerting} and Rasmussen, {Peter Mondrup} and Nyengaard, {Jens Randel} and J{\o}rgensen, {Malene M{\o}ller} and {de Paoli}, Frank and B{\o}tker, {Hans Erik} and J{\o}rgen Kjems and Kristian Vissing and Drasbek, {Kim Ryun}",

year = "2022",

month = mar,

doi = "10.3390/ijms23063334",

language = "English",

volume = "23",

journal = "International Journal of Molecular Sciences ",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "6",

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Gu, T, Just, J , Stenz, KT, Yan, Y, Sieljacks, P, Wang, J, Groennebaek, TS, Jakobsgaard, JE , Rindom, E , Herskind, J, Gravholt, A, Lassen, TR, Jørgensen, M, Bæk, R, Gutiérrez-Jiménez, E, Iversen, NK, Rasmussen, PM , Nyengaard, JR, Jørgensen, MM, de Paoli, F , Bøtker, HE , Kjems, J , Vissing, K & Drasbek, KR 2022, 'The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance', International Journal of Molecular Sciences , vol. 23, no. 6, 3334. https://doi.org/10.3390/ijms23063334

The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance. / Gu, Tingting; Just, Jesper ; Stenz, Katrine Tang et al.
In: International Journal of Molecular Sciences , Vol. 23, No. 6, 3334, 03.2022.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance

AU - Gu, Tingting

AU - Just, Jesper

AU - Stenz, Katrine Tang

AU - Yan, Yan

AU - Sieljacks, Peter

AU - Wang, Jakob

AU - Groennebaek, Thomas Skjaerlund

AU - Jakobsgaard, Jesper Emil

AU - Rindom, Emil

AU - Herskind, Jon

AU - Gravholt, Anders

AU - Lassen, Thomas Ravn

AU - Jørgensen, Mathias

AU - Bæk, Rikke

AU - Gutiérrez-Jiménez, Eugenio

AU - Iversen, Nina Kerting

AU - Rasmussen, Peter Mondrup

AU - Nyengaard, Jens Randel

AU - Jørgensen, Malene Møller

AU - de Paoli, Frank

AU - Bøtker, Hans Erik

AU - Kjems, Jørgen

AU - Vissing, Kristian

AU - Drasbek, Kim Ryun

PY - 2022/3

Y1 - 2022/3

N2 - Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification.

AB - Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification.

KW - Angiogenesis

KW - Brain ischemia

KW - Cell viability

KW - Human brain vascular endothelial cells

KW - Infarction

KW - Plasma extracellular vesicles

KW - Remote ischemic conditioning

KW - Resistance exercise

KW - Stroke

KW - MOUSE-BRAIN

KW - human brain vascular endothelial cells

KW - INJURY

KW - infarction

KW - remote ischemic conditioning

KW - plasma extracellular vesicles

KW - CEREBRAL-ISCHEMIA

KW - brain ischemia

KW - MECHANISM

KW - angiogenesis

KW - PREVENTION

KW - BLOOD-FLOW

KW - stroke

KW - HEART

KW - cell viability

KW - MODELS

KW - EXOSOMES

KW - resistance exercise

KW - CELL

U2 - 10.3390/ijms23063334

DO - 10.3390/ijms23063334

M3 - Journal article

C2 - 35328755

SN - 1661-6596

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 6

M1 - 3334

ER -

The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance

Abstract

Keywords

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