Compromised endothelial progenitor cell exosomal communication with endothelial cells in hypertension ischemia conditions

Abstract

BackgroundWe have previously demonstrated that EPC‐exosomes (EPC‐EXs) can protect endothelial cells (ECs) against hypoxia injury in vitro. What's more, we found that extracellular vesicles released from starved EPCs have opposite functions to those released in inflammation conditions, suggesting that EPC‐EXs‐mediated communication is functional and modulable by factors that affect the status of their parent cells. Given clinical studies showing the function of EPCs is declined in patients with hypertension, we speculate the EPC‐EX mediated communication with ECs is impaired in hypertension‐ischemia conditions.MethodsEPC‐EXs were prepared from the bone marrow EPCs of wild type (WT) and hypertensive renin transgene (R+) mice and were denoted as WT‐EPC‐EXs and R‐EPC‐EXs, respectively. To mimic hypertension‐ischemia injury, ECs were treated with angiotensin II (10‐6 M) plus hypoxia (1% O2 for 6 hrs) and reoxygenation (21% O2 for 24 hrs). To determine the function of EPC‐EXs, ECs were co‐cultured with EXs for 24hrs. EX uptake efficiency, cellular viability and function were assessed.Results1) The incorporation efficiency of EPC‐EXs from R+ mice by ECs were decreased. 2) Angiotensin II plus hypoxia reoxygenation‐injured ECs displayed decreased cell viability, increased cell apoptosis and compromised angiogenic ability. 3) R‐EPC‐EXs displayed the impaired capability of rescuing ECs and improving their angiogenic ability on ECs as compared to that of WT‐EPC‐EXs did.ConclusionOur data have suggested that EPC‐EXs mediated communication of EPC/EC is compromised in R+ mice hypertension‐ischemia conditions. These findings suggest that impairment of EPC exosomal communication might contribute to the exaggerated cerebral ischemia injury in hypertension‐associated ischemic stroke.