title: Differential microRNA expression profiles in peripheral arterial disease.
abstract: BACKGROUND
  Peripheral arterial disease (PAD) is a clinical condition caused by an atherosclerotic process affecting the arteries of the limbs. Despite major improvements in surgical endovascular techniques, PAD is still associated with high mortality and morbidity. Recently, microRNAs (miRNAs), a class of short noncoding RNA controlling gene expression, have emerged as major regulators of multiple biological processes.
  
  
  RESULTS
  A whole-miRNA transcriptome profiling was performed in peripheral blood from an initial sample set of patients and controls. A 12-miRNA PAD-specific signature, which includes let 7e, miR-15b, -16, -20b, -25, -26b, -27b, -28-5p, -126, -195, -335, and -363, was further investigated and validated in 2 additional sample sets. Each of these 12 miRNAs exhibited good diagnostic value as evidenced by receiver operating characteristic curve analyses. Pathway enrichment analysis using predicted and validated targets identified several signaling pathways relevant to vascular disorders. Several of these pathways, including cell adhesion molecules, were confirmed by quantifying the expression level of several candidate genes regulating the initial stages of the inflammatory atherosclerotic process. The expression level of 7 of these candidate genes exhibits striking inverse correlation with that of several, if not all, of the miRNAs of the PAD-specific miRNA signature.
  
  
  CONCLUSIONS
  These results demonstrate the potential of miRNAs for the diagnosis of PAD and provide further insight into the molecular mechanisms leading to the development of PAD, with the potential for future therapeutic targets.
authors.affiliation: Department of Cardiovascular Sciences and Department of Genetics and the NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Stather
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sylvius
authors.forename: John B
authors.initials: JB
authors.lastname: Wild
authors.forename: Edward
authors.initials: E
authors.lastname: Choke
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sayers
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bown
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: biological markers; microRNAs; peripheral artery disease; peripheral vascular diseases; vascular diseases