title: Plexiform vasculopathy of severe pulmonary arterial hypertension and microRNA expression.
abstract: BACKGROUND
  Recent studies have revealed that microRNAs (miRNAs) play a key role in the control of angiogenesis and vascular remodeling. Specific miRNAs in plexiform vasculopathy of severe pulmonary arterial hypertension (PAH) in humans have not yet been investigated.
  
  
  METHODS
  We analyzed expression of miR-143/145 (vascular smooth muscle-specific), miR-126 (endothelial-specific) and related mRNAs in plexiform (PLs) and concentric lesions (CLs), which had been laser-microdissected from specimens of formalin-fixed, paraffin-embedded, explanted lungs of PAH patients (n = 12) and unaffected controls (n = 8). Samples were analyzed by real-time polymerase chain reaction, and protein expression was determined by immunohistochemistry.
  
  
  RESULTS
  Expression levels of miR-143/145 and its target proteins (e.g., myocardin, smooth muscle myosin heavy chain) were found to be significantly higher in CLs than in PLs, whereas miR-126 and VEGF-A were significantly up-regulated in PLs when compared with CLs, indicating a more prominent angiogenic phenotype of PL. This correlates with a down-regulation of miR-204 as well as an up-regulation of miR-21 in PLs, which in turn corresponds to enhanced cell proliferation.
  
  
  CONCLUSIONS
  Our findings show that morphologic changes of plexiform vasculopathy in the end-stage PAH lung are reflected by alterations at the miRNA level.
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany. bockmeyer.clemens@mh-hannover.de
authors.forename: Clemens L
authors.initials: CL
authors.lastname: Bockmeyer
authors.forename: Lavinia
authors.initials: L
authors.lastname: Maegel
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.forename: Johanna
authors.initials: J
authors.lastname: Rische
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
authors.forename: Nils
authors.initials: N
authors.lastname: Nickel
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
authors.forename: Heiko A
authors.initials: HA
authors.lastname: Golpon
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Florian
authors.initials: F
authors.lastname: Laenger
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D015854:Up-Regulation; D014652:Vascular Diseases / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: C527111:MIRN126 microRNA, human; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A