title: Upregulation of miR-483-3p contributes to endothelial progenitor cells dysfunction in deep vein thrombosis patients via SRF.
abstract: BACKGROUND
  Endothelial progenitor cells (EPCs) contribute to recanalization of deep vein thrombosis (DVT). This study aimed to detect miRNA expression profiles in EPCs from patients with DVT and characterize the role of miRNA in EPCs dysfunction.
  
  
  METHODS
  EPCs was isolated from DVT patients and control subjects, and miRNA expression profiles were compared to screen differential miRNAs. The candidate miRNAs were confirmed by RT-PCR analysis. The targets of miRNA were identified by bioinformatics analyses, luciferase reporter assay and gene expression analyses. The apoptosis, migration and tube formation of EPCs were examined by flow cytometry, transwell assay and matrigel tube formation assay. A rat model of venous thrombosis was established as in vivo model.
  
  
  RESULTS
  We identified miR-483-3p as a candidate miRNA upregulated in EPCs from DVT patients. By using miR-483-3p agomir and antagomir, we demonstrated that miR-483-3p decreased the migration and tube formation while increased the apoptosis of EPCs. Moreover, we identified serum response factor (SRF) as the target of miR-483-3p, and showed that SRF knockdown decreased the migration and tube formation while increased the apoptosis of EPCs. In addition, miR-483-3p inhibition led to enhanced ability of homing and thrombus resolution of EPCs in rat model of venous thrombosis.
  
  
  CONCLUSIONS
  miR-483-3p is upregulated in EPCs from DVT patients, and it targets SRF to decrease EPCs migration and tube formation and increase apoptosis in vitro, while decrease EPCs homing and thrombus resolution in vivo. MiR-483-3p is a potential therapeutic target in DVT treatment.
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. 538600@163.com.
authors.forename: Lingshang
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. 921124978@qq.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. dd0341@163.com.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. 1136250110@qq.com.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. 1131612767@qq.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. nmy0552@126.com.
authors.forename: Wendong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. weisen321@qq.com.
authors.forename: Sen
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. 547061881@qq.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. 563677272@qq.com.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Rd, Suzhou, 215000, Jiangsu, China. ning2005@139.com.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D002465:Cell Movement / Q000235:genetics; D002469:Cell Separation; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D026362:Serum Response Factor / Q000378:metabolism*; D013927:Thrombosis / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics* / Q000503:physiopathology*
chemical_list: C548912:MIRN483 microRNA, human; D035683:MicroRNAs; D026362:Serum Response Factor