Abstract 3582: Proteomic Profiling Reveals Significantly Altered Right Ventricular Protein Expression and Phosphorylation Patterns in Experimental Tachycardia-induced Heart Failure
Background: While current heart failure (HF) research mainly focuses on pathological left ventricular alterations, the involvement of right ventricle (RV) is much less clearly analyzed. In our project we applied a proteomic approach to a rabbit model of tachycardia-induced HF to detect differences in RV protein expression and phosphorylation patterns.
Methods: After inserting pacemaker leads transjugularly and implanting pacemaker aggregates subcutaneously in rabbits, HF was induced by chronic progressive pacing, starting at 330 beats per minute, then 360 bpm, and finally 380 bpm for 10 days each (congestive HF, CHF). During pacing, invasive blood pressure was determined and animals underwent echocardiography repeatedly. Untreated animals served as controls (CTRL). RV tissue of CTRL and CHF animals (n=4, respectively) was subjected to 2D-gel electrophoresis. Differentially expressed proteins were identified via mass spectrometry using a specifically developed identification algorithm. Differences in global phosphorylation patterns were revealed by phosphoprotein staining.
Results: CHF was characterized by significantly decreased mean arterial pressure, LV dysfunction and dilatation as well as by atrial and RV hypertrophy (all p<0.01 vs. CTRL). From RV preparations of animals with CHF, significantly altered protein expression patterns could be detected as compared to CTRL reflecting changes in at least 4 cellular pathways (p<0.05 vs. CTRL for each protein):
oxidative phosphorylation (NADH dehydrogenase FeS protein, NADH dehydrogenase subunit),
metabolic pathways (glutathion S-transferase, dimethylarginine dimethylaminohydrolase 1, dihydrolipoamide S-succinyltransferase),
antioxidant enzymes (peroxiredoxin 6), and 4. calcium-signalling (sarcoplasmic reticulum glycoprotein).
Finally, significant differences in global protein phosphorylation patterns could be identified.
Conclusions: Right ventricle is involved in progressive tachycardia-induced heart failure as indicated by significantly altered RV protein expression patterns reflecting changes in diverse cellular pathways. Additional alterations in global phosphorylation patterns may also suggest major changes in functional protein status.