title: Proteomics analysis of cardiac extracellular matrix remodeling in a porcine model of ischemia/reperfusion injury.
abstract: BACKGROUND
  After myocardial ischemia, extracellular matrix (ECM) deposition occurs at the site of the focal injury and at the border region.
  
  
  RESULTS
  We have applied a novel proteomic method for the analysis of ECM in cardiovascular tissues to a porcine model of ischemia/reperfusion injury. ECM proteins were sequentially extracted and identified by liquid chromatography tandem mass spectrometry. For the first time, ECM proteins such as cartilage intermediate layer protein 1, matrilin-4, extracellular adipocyte enhancer binding protein 1, collagen α-1(XIV), and several members of the small leucine-rich proteoglycan family, including asporin and prolargin, were shown to contribute to cardiac remodeling. A comparison in 2 distinct cardiac regions (the focal injury in the left ventricle and the border region close to the occluded coronary artery) revealed a discordant regulation of protein and mRNA levels; although gene expression for selected ECM proteins was similar in both regions, the corresponding protein levels were much higher in the focal lesion. Further analysis based on >100 ECM proteins delineated a signature of early- and late-stage cardiac remodeling with transforming growth factor-β1 signaling at the center of the interaction network. Finally, novel cardiac ECM proteins identified by proteomics were validated in human left ventricular tissue acquired from ischemic cardiomyopathy patients at cardiac transplantation.
  
  
  CONCLUSIONS
  Our findings reveal a biosignature of early- and late-stage ECM remodeling after myocardial ischemia/reperfusion injury, which may have clinical utility as a prognostic marker and modifiable target for drug discovery.
authors.affiliation: King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London, UK.
authors.forename: Javier
authors.initials: J
authors.lastname: Barallobre-Barreiro
authors.forename: Athanasios
authors.initials: A
authors.lastname: Didangelos
authors.forename: Friedrich A
authors.initials: FA
authors.lastname: Schoendube
authors.forename: Ignat
authors.initials: I
authors.lastname: Drozdov
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.forename: Mariana
authors.initials: M
authors.lastname: Fernández-Caggiano
authors.forename: Peter
authors.initials: P
authors.lastname: Willeit
authors.forename: Valentina O
authors.initials: VO
authors.lastname: Puntmann
authors.forename: Guillermo
authors.initials: G
authors.lastname: Aldama-López
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
authors.forename: Nieves
authors.initials: N
authors.lastname: Doménech
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
mesh_terms: D000818:Animals; D015415:Biomarkers; D002853:Chromatography, Liquid; D055808:Drug Discovery; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005355:Fibrosis; D020869:Gene Expression Profiling; D016027:Heart Transplantation; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D040901:Proteomics; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D034421:Sus scrofa; D013552:Swine; D053719:Tandem Mass Spectrometry; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D020257:Ventricular Remodeling / Q000235:genetics / Q000502:physiology
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1