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

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. © 2011 petrak et al; licensee biomed central ltd.