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2018 ; 22
(3
): 1873-1882
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ACE2-EPC-EXs protect ageing ECs against hypoxia/reoxygenation-induced injury
through the miR-18a/Nox2/ROS pathway
#MMPMID29363860
Zhang C
; Wang J
; Ma X
; Wang W
; Zhao B
; Chen Y
; Chen C
; Bihl JC
J Cell Mol Med
2018[Mar]; 22
(3
): 1873-1882
PMID29363860
show ga
Oxidative stress is one of the mechanisms of ageing-associated vascular
dysfunction. Angiotensin-converting enzyme 2 (ACE2) and microRNA (miR)-18a have
shown to be down-regulated in ageing cells. Our previous study has shown that
ACE2-primed endothelial progenitor cells (ACE2-EPCs) have protective effects on
endothelial cells (ECs), which might be due to their released exosomes (EXs).
Here, we aimed to investigate whether ACE2-EPC-EXs could attenuate
hypoxia/reoxygenation (H/R)-induced injury in ageing ECs through their carried
miR-18a. Young and angiotensin II-induced ageing ECs were subjected to H/R and
co-cultured with vehicle (medium), EPC-EXs, ACE2-EPCs-EXs, ACE2-EPCs-EXs + DX600
or ACE2-EPCs-EXs with miR-18a deficiency (ACE2-EPCs-EXs(anti-miR-18a) ). Results
showed (1) ageing ECs displayed increased senescence, apoptosis and ROS
production, but decreased ACE2 and miR-18a expressions and tube formation
ability; (2) under H/R condition, ageing ECs showed higher rate of apoptosis, ROS
overproduction and nitric oxide reduction, up-regulation of Nox2, down-regulation
of ACE2, miR-18a and eNOS, and compromised tube formation ability; (3) compared
with EPC-EXs, ACE2-EPC-EXs had better efficiencies on protecting ECs from
H/R-induced changes; (4) The protective effects were less seen in ACE2-EPCs-EXs +
DX600 and ACE2-EPCs-EXs(anti-miR-18a) groups. These data suggest that
ACE-EPCs-EXs have better protective effects on H/R injury in ageing ECs which
could be through their carried miR-18a and subsequently down-regulating the
Nox2/ROS pathway.