title: microRNA-222 controls neovascularization by regulating signal transducer and activator of transcription 5A expression.
abstract: OBJECTIVE
  Inflammatory stimuli released into atherosclerotic plaque microenvironment regulate vessel formation by modulating gene expression and translation. microRNAs are a class of short noncoding RNAs, acting as posttranscriptional regulators of protein-coding genes involved in various biological processes, including vascular cell biology. Among them, microRNA-221/222 (miR-221/222) seem to negatively modulate vascular remodeling by targeting different target genes. Here, we investigated their potential contribution to inflammation-mediated neovessel formation.
  
  
  RESULTS
  We used quantitative real-time RT-PCR amplification to analyze expression of 7 microRNAs previously linked to vascular biology, such as miR-17-5p, miR-21, miR-126, miR-210, miR-221, miR-222, and miR-296 and found high levels of expression for all of them in quiescent endothelial cells. However, miR-126, miR-221, miR-222, and miR-296 turned out to be down-modulated in endothelial cells exposed to inflammatory stimuli. Applying a gain-of-function approach, we demonstrated that, among them, only miR-222 was involved in inflammation-mediated vascular remodeling. In addition, we identified signal transducer and activator of transcription 5A (STAT5A) as a bona fide target of miR-222 and observed that miR-222 negatively correlated with STAT5A expression in human endothelial cells from advanced neovascularized atherosclerotic lesions.
  
  
  CONCLUSIONS
  We identified STAT5A as a novel miR-222 target, and this finding opens up new perspectives for treatment of vascular diseases.
authors.affiliation: Department of Internal Medicine, University of Torino, Torino, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dentelli
authors.forename: Arturo
authors.initials: A
authors.lastname: Rosso
authors.forename: Francesca
authors.initials: F
authors.lastname: Orso
authors.forename: Cristina
authors.initials: C
authors.lastname: Olgasi
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.forename: Maria Felice
authors.initials: MF
authors.lastname: Brizzi
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000235:genetics; D034622:RNA Interference; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D016222:Fibroblast Growth Factor 2; D018836:Inflammation Mediators; D007377:Interleukin-3; D035683:MicroRNAs; D050799:STAT5 Transcription Factor; D025521:Tumor Suppressor Proteins; C508596:IL3 protein, human; C525709:MIR221, human; C525710:MIR222, human; C494092:STAT5A protein, human