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10.1111/jcmm.13471

http://scihub22266oqcxt.onion/10.1111/jcmm.13471
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suck abstract from ncbi


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pmid29363860
      J+Cell+Mol+Med 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.
  • |Angiotensin-Converting Enzyme 2 [MESH]
  • |Animals [MESH]
  • |Antagomirs/genetics/metabolism [MESH]
  • |Apoptosis/drug effects [MESH]
  • |Cell Differentiation/drug effects [MESH]
  • |Cell Hypoxia [MESH]
  • |Cell Movement/drug effects [MESH]
  • |Cell Proliferation/drug effects [MESH]
  • |Cellular Senescence/drug effects [MESH]
  • |Endothelial Progenitor Cells/cytology/*drug effects/metabolism [MESH]
  • |Exosomes/*chemistry/metabolism [MESH]
  • |Gene Expression Regulation [MESH]
  • |Mice [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |MicroRNAs/*genetics/metabolism [MESH]
  • |NADPH Oxidase 2/*genetics/metabolism [MESH]
  • |Nitric Oxide Synthase Type III/genetics/metabolism [MESH]
  • |Nitric Oxide/metabolism [MESH]
  • |Oxygen/pharmacology [MESH]
  • |Peptides/pharmacology [MESH]
  • |Peptidyl-Dipeptidase A/*genetics/metabolism [MESH]
  • |Primary Cell Culture [MESH]
  • |Reactive Oxygen Species/*metabolism [MESH]


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