title: Expression of the FAST-1 transcription factor in coronary artery transplant vasculopathy and activated vascular smooth muscle cells.
abstract: BACKGROUND
  The activation of vascular smooth muscle cells (VSMCs) causes most of the obliterative vasculopathy responsible for solid-organ allograft failure. Identification of genes expressed in activated VSMCs may provide clues to the pathogenesis and progression of cardiac allograft vasculopathy (CAV).
  
  
  METHODS
  We performed cDNA micro-array analysis of mRNA isolated from a healthy human coronary artery, from a coronary artery from a patient with CAV, and from quiescent and stimulated cultured human coronary artery VSMCs. Western blot analysis and immunohistochemistry verified fork-head activin signal transducer 1 (FAST-1) expression.
  
  
  RESULTS
  Fold-change analysis determined that increased expression of a transcription factor involved in transforming growth factor beta (TGF-beta) signaling, FAST-1, was induced in arteries with CAV and in activated VSMCs, compared with normal and unstimulated cells. Western blotting confirmed increased FAST-1 expression in arteries with CAV vs normal arteries and arteries from failing hearts and confirmed increased expression in cultured VSMCs stimulated with a variety of cytokines. Immunohistochemical analysis determined that FAST-1 expression localized to neo-intimal VSMCs in rejecting arteries. In cultured VSMCs, FAST-1 immunolocalizes to the nucleus after TGF-beta stimulation.
  
  
  CONCLUSIONS
  These results demonstrate differential expression of the FAST-1 gene in the VSMC response to inflammatory stimuli. Considering the significant role of TGF-beta in vascular fibroproliferative diseases, this work suggests that FAST-1 may participate in the VSMC response to injury and may represent a potential molecular target for modulating the progression of CAV.
authors.affiliation: Department of Cardiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Sheri F
authors.initials: SF
authors.lastname: Kelemen
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Eisen
authors.forename: Michael V
authors.initials: MV
authors.lastname: Autieri
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D006331:Heart Diseases / Q000378:metabolism*; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C510350:FOXH1 protein, human; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D014157:Transcription Factors