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 Groennebaek, Jesper Emil Jakobsgaard, Emil Rindom, Jon Herskind, Anders Gravholt, Thomas Ravn Lassen, Mathias Jo̷rgensen, Rikke Bæk, Eugenio Gutiérrez‐Jiménez, Nina Iversen, Peter Mondrup Rasmussen, Jens Randel Nyengaard, Maléne Møller Jørgensen, Frank Vincenzo de Paoli, Hans Erik Bøtker, Jørgen Kjems, Kristian Vissing, Kim Ryun Drasbek
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.