title: A dysregulated microRNA-26a/EphA2 axis impairs endothelial progenitor cell function via the p38 MAPK/VEGF pathway.
abstract: BACKGROUND
  Dysfunction of circulating endothelial progenitor cells (EPCs) is associated with the onset of cardiovascular disorders. Circulating microRNAs (miRNAs) have been recognized as novel biomarkers and potential therapeutic targets. Here, we examined the role of miR-26a overexpression in atherosclerosis and explored the underlying mechanisms.
  
  
  METHODS
  EPCs were obtained from patients with atherosclerosis and healthy controls. Bone marrow (BM)-derived EPCs were exposed to hypoxia to mimic the atherosclerotic environment and miR-26a, EphA2 and p38 MAPK levels were measured by qRT-PCR and western blotting, and VEGF levels were determined by enzyme linked immunosorbent assay. Cell viability was assessed using the MTT assay, and luciferase activity assays confirmed EphA2 as a target of miR-26a.
  
  
  RESULTS
  MiR-26a was overexpressed in patients with atherosclerosis and associated with EPC dysfunction. EphA2 was identified as a direct target of miR-26a. Overexpression of miR-26a downregulated EphA2 and impaired EPC function, whereas knockdown of miR-26a upregulated EphA2 and reversed hypoxia-induced EPC dysfunction. MiR-26a overexpression or knockdown modulated the activity of p38 MAPK and the levels of VEGF in EPCs.
  
  
  CONCLUSIONS
  The role of miR-26a in atherosclerosis is mediated by its target EphA2 via a mechanism involving the p38 MAPK/VEGF pathway.
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zuo
authors.forename: Kangkang
authors.initials: K
authors.lastname: Zhi
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Chenghui
authors.initials: C
authors.lastname: Lu
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics; D001665:Binding Sites; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D051381:Rats; D036104:Receptor, EphA2 / Q000097:blood* / Q000235:genetics*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D036104:Receptor, EphA2; D042461:Vascular Endothelial Growth Factor A; C528163:MIRN26 microRNA, human; C467484:VEGFA protein, human