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
| Autor: | David Sedmera, Ondrej Vit, Ludek Cervenka, Petr L. Jedelsky, Lucie Lorkova, Hynek Strnad, Jan Benes, Jana Pospisilova, Miroslava Šedinová, Jiri Petrak, Michal Kolar, Vojtech Melenovsky |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
biology
lcsh:Cytology Monoamine oxidase Tissue transglutaminase Research Volume overload Heart failure Proteomics Bioinformatics Ryanodine receptor 2 Biochemistry annexins Cell biology Transcriptome transglutaminase Downregulation and upregulation biology.protein monoamine oxidase lcsh:QH573-671 Monoamine oxidase A hypertrophy Molecular Biology |
| Zdroj: | Proteome Science, Vol 9, Iss 1, p 69 (2011) Proteome Science |
| ISSN: | 1477-5956 |
| DOI: | 10.1186/1477-5956-9-69 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|