High-intensity interval training improves the function of exosomes derived from endothelial progenitor cells in spontaneously hypertensive rats

Lu Anran; Wang Chenyu; Zhang Yan; Huang Huasheng

doi:10.12307/2026.713

Abstract：BACKGROUND:Under hypertensive conditions,exosome communication between endothelial progenitor cells and brain endothelial cells is impaired,which may be a key mechanism leading to poor prognosis in patients with hypertensive stroke.Exercise rehabilitation is an important non-drug means of preventing and treating hypertensive stroke,but the specific mechanism is unclear. OBJECTIVE:To investigate the effect of high-intensity interval training on the function of exosomes from endothelial progenitor cells in spontaneously hypertensive rats and explore the possible mechanism. METHODS:Twenty-four male spontaneously hypertensive rats were randomly assigned into exercise group or control group.The animals in the exercise group underwent 6 weeks of high-intensity interval training,while those in the control group were kept quietly in cage.After the experiment,bone marrow endothelial progenitor cells were isolated and cultured,and exosomes were obtained to detect the expression of miR-27a using qPCR.After treating neuroblastoma N2a(Neuro-2a)with angiotensin Ⅱ and hypoxia,they were co-incubated with endothelial progenitor cell-derived exosomes and a miR-27a inhibitor.The cells were then divided into the following groups:a blank group(cultured in normoxic high-glucose DMEM medium),an injury group(treated with angiotensin Ⅱ combined with hypoxia),an injury+control exosome group,an injury+exercise exosome group,and an injury+exercise exosome+miR-27a inhibitor group.The following parameters were assessed:exosome uptake rate,cell viability,reactive oxygen species levels,and the expression levels of cytochrome C and NADPH oxidase 4 protein. RESULTS AND CONCLUSION:(1)Exercise could increase the uptake efficiency of endothelial progenitor cell exosomes by Neuro-2a cells.(2)Exercise up-regulated the expression of miR-27a in endothelial progenitor cell exosomes and Neuro-2a cells(P<0.05).(3)Exercise-induced endothelial progenitor cell exosomes improved the survival of Neuro-2a cells(P<0.05),reduced the level of reactive oxygen species(P<0.05)and down-regulated the protein expression of cytochrome C and NADPH oxidase 4(P<0.05),while the above effects were weakened after administration of miR-27a inhibitor(P<0.05).To conclude,high-intensity interval training-induced exosomes from endothelial progenitor cells in spontaneously hypertensive rats alleviate the oxidative stress of damaged neurons through the miR-27a pathway.