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Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2.

ABSTRACT: BACKGROUND:Chronic hemodynamic overloading leads to heart failure (HF) due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF) and sham-operated rats harvested at the advanced, decompensated stage of HF. METHODS:We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip. RESULTS:In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs. CONCLUSIONS:The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy.

SUBMITTER: Petrak J

PROVIDER: S-EPMC3225319 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2.

Petrak Jiri J Pospisilova Jana J Sedinova Miroslava M Jedelsky Petr P Lorkova Lucie L Vit Ondrej O Kolar Michal M Strnad Hynek H Benes Jan J Sedmera David D Cervenka Ludek L Melenovsky Vojtech V

Proteome science 20111111 1

<h4>Background</h4>Chronic hemodynamic overloading leads to heart failure (HF) due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF) and sham-operated rats harvested at the advanced, decompensated stage of HF.<h ...[more]

PMID: 22078724

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Project description:BackgroundAorta-pulmonary (A-P) artery fistula following a stab wound to the chest with superimposed infective endocarditis (IE) is a rare, often unrecognized presentation. Herein, we report a case of A-P fistula due to stab chest assessed by two- and three-dimensional (3D) imaging.Case summaryA 30-year-old man presented with a history of being stabbed in the chest with a screwdriver. The chest wall laceration was sutured, an intercostal drain inserted for a haemopneumothorax, and he was subsequently discharged. He presented 3 weeks later with exertional dyspnoea, fever, rigours, and loss of weight. On examination, he had a wide pulse pressure and a harsh continuous murmur in the 2nd left intercostal space associated with a palpable thrill. Blood tests revealed raised infective markers and anaemia. All blood cultures were sterile. On echocardiography, the aortic and pulmonary valve was severely damaged, with suspicion of superimposed vegetations secondary to IE. There was severe aortic and pulmonary valve regurgitation. A fistulous connection was noted between the aorta and main pulmonary artery, just below the commissure adjoining the right and left coronary sinus of the aortic valve. On 3D imaging, the defect was quantified. The patient was subsequently referred for aortic and pulmonary valve replacement and closure of the A-P fistula. The presence of multiple vegetations was confirmed intraoperatively. He also received a 6-week course of intravenous antibiotics.DiscussionWe have described a rare case of an A-P fistula due to a stab wound to the chest complicated by IE. In a patient with stab wound to the chest, a high index of suspicion of cardiac involvement must be maintained, and a careful search for intracardiac shunts must be made on echocardiography, prior to discharge. Furthermore, in addition to two-dimensional imaging, 3D imaging proved useful in providing a comprehensive assessment of the morphology of the lesion prior to surgery.

Dataset Information

Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2.

Publications

Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2.

Similar Datasets

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