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

BackgroundFew 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 ResultsHeart 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).ConclusionsOur 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.

Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy

“…We identified SORBS2 as a major direct target of miR-21*. In line, SORBS2 was detected recently in human heart tissue and was found to be repressed in cardiac pathologies (28). SORBS2 is localized in the Z-bands of mature myofibrils and regulates important processes in cardiomyocytes, including the assembly of myofibrils or regulation of signaling at the Z-band level (27).…”

“…Among them, sorbin and SH3 domain-containing protein 2 (SORBS2) was strongly silenced and a very interesting candidate (Table 1), as SORBS2 was predicted to have 2 miRNA recognition sites in the 3′UTR for miR-21*. Indeed, SORBS2, also known as Arg-binding protein 2 (ARGBP2), is expressed at high levels in the heart and is repressed during cardiac pathologies (27,28). We revealed that transfection of miR-21* in cardiomyocytes led to repression of SORBS2 protein expression, which was not observed after transfection of miR-21 ( Figure 4, C and D).…”

Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy

“…SORBS2 localizes to Z-disks, in which it influences the contractile and elastic properties of cardiac sarcomeres (22). Interestingly, release of SORBS2 from damaged cardiac tissue into the bloodstream upon fatal acute myocardial infarction has been described recently (23). PDLIM5 is highly conserved across species and, like SORBS2, colocalizes at Z-disks and is directly associated with dilated cardiomyopathy (24) and indirectly involved in human hypertrophic cardiomyopathy (25).…”

Does the Rewarmed Heart Restore the Myocardial Proteome to That of the Pre-Cooled State? – A Proteomic Analysis of Surgical Samples –

“…39 When severe IR injury occurs, SORBS2 proteins are released from the heart into the bloodstream after reperfusion. 40 However, we could not detect SORBS2 protein in plasma taken after reperfusion in our previous proteomic analysis. 14 The 7 isoforms of 14-3-3 proteins have multiple roles in the apoptotic signaling network and work for signaling integration.…”