Abstract

Sorbin and SH3 Domain‐Containing Protein 2 Is Released from Infarcted Heart in the Very Early Phase: Proteomic Analysis of Cardiac Tissues From Patients

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 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.

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Kakimoto Y, Ito S, Abiru H, Kotani H, Ozeki M, Tamaki K, and Tsuruyama T:
Sorbin and SH3 Domain‐Containing Protein 2 is Released from Infarcted Heart in the Very Early Phase: Proteomic Analysis of Cardiac Tissues From Patients

J. Am. Heart Assoc. 2: e000565 (2013); originally published 16.12.2013; doi: 10.1161/​JAHA.113.000565

In the course of this study the authors utilized laser microdissection to sample infarcted and healthy human cardiac tissue on a square millimeter scale. A very high sampling accuracy was needed because of subsequent proteomic analysis (LC-MS/MS) of the histologic samples, which is a highly sensitive method. Laser microdissection was used in this case to exclude unwanted tissue areas – like large capillaries or areas of fibrosis – that would distort mass spectrometric results.

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