Open AccessSorbin and SH 3 Domain‐Containing Protein 2 Is Released From Infarcted Heart in the Very Early Phase: Proteomic Analysis of Cardiac Tissues From Patients
Author(s) -
Kakimoto Yu,
Ito Shinji,
Abiru Hitoshi,
Kotani Hirokazu,
Ozeki Munetaka,
Tamaki Keiji,
Tsuruyama Tatsuaki
Publication year - 2013
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.113.000565
Subject(s) - myocardial infarction , medicine , laser capture microdissection , western blot , biomarker , proteomics , immunohistochemistry , infarction , pathology , cardiology , gene expression , biology , biochemistry , gene
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. Methods and 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 SH 3 domain‐containing protein 2 ( SORBS 2) 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 SH 3 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 SH 3 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.