title: Sorbin and SH3 domain-containing protein 2 is released from infarcted heart in the very early phase: proteomic analysis of cardiac tissues from patients.
abstract: BACKGROUND
  Few proteomic studies have examined human cardiac tissue following acute lethal infarction. Here, we applied a novel proteomic approach to formalin-fixed, paraffin-embedded human tissue and aimed to reveal the molecular changes in the very early phase of acute myocardial infarction.
  
  
  RESULTS
  Heart tissue samples were collected from 5 patients who died within 7 hours of myocardial infarction and from 5 age- and sex-matched control cases. Infarcted and control myocardia were histopathologically diagnosed and captured using laser microdissection. Proteins were extracted using an originally established method and analyzed using liquid chromatography-tandem mass spectrometry. The label-free quantification demonstrated that the levels of 21 proteins differed significantly between patients and controls. In addition to known biomarkers, the sarcoplasmic protein sorbin and SH3 domain-containing protein 2 (SORBS2) was greatly reduced in infarcted myocardia. Immunohistochemical analysis of cardiac tissues confirmed the decrease, and Western blot analysis showed a significant increase in serum sorbin and SH3 domain-containing protein 2 in acute myocardial infarction patients (n=10) compared with control cases (n=11).
  
  
  CONCLUSIONS
  Our advanced comprehensive analysis using patient tissues and serums indicated that sarcoplasmic sorbin and SH3 domain-containing protein 2 is released from damaged cardiac tissue into the bloodstream upon lethal acute myocardial infarction. The proteomic strategy presented here is based on precise microscopic findings and is quite useful for candidate biomarker discovery using human tissue samples stored in depositories.
authors.affiliation: Department of Forensic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kakimoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Ito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Abiru
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kotani
authors.forename: Munetaka
authors.initials: M
authors.lastname: Ozeki
authors.forename: Keiji
authors.initials: K
authors.lastname: Tamaki
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D002423:Cause of Death; D002853:Chromatography, Liquid; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D018398:Homeodomain Proteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D016612:Paraffin Embedding; D040901:Proteomics / Q000379:methods; D016601:RNA-Binding Proteins; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D016707:Tissue Fixation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D005404:Fixatives; D018398:Homeodomain Proteins; D016601:RNA-Binding Proteins; C490755:SORBS2 protein, human; D005557:Formaldehyde
keywords: SORBS2; myocardial infarction; proteomics; tissue