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  • Title: Proteomic profiling implies mitochondrial dysfunction in tachycardia-induced heart failure.
    Author: Birner C, Dietl A, Deutzmann R, Schröder J, Schmid P, Jungbauer C, Resch M, Endemann D, Stark K, Riegger G, Luchner A.
    Journal: J Card Fail; 2012 Aug; 18(8):660-73. PubMed ID: 22858083.
    Abstract:
    BACKGROUND/OBJECTIVES: Molecular mechanisms of congestive heart failure as reflected by alterations of protein expression patterns are still incompletely analyzed. We therefore investigated intraventricular (ie, left ventricular congestive heart failure [LV-CHF] vs. LV-control [CTRL], and right ventricular [RV]-CHF vs. RV-CTRL) and interventricular (ie, LV-CHF vs. RV-CHF, and LV-CTRL vs. RV-CTRL) protein expression differences in an animal model. METHODS: The model of rapid ventricular pacing in rabbits was combined with a proteomic approach using 2-dimensional gel electrophoresis. Identification of proteins was done by matrix-assisted laser desorption/ionization-tandem mass spectrometry (MALDI-MS/MS). RESULTS: Rapid ventricular pacing-induced heart failure was characterized by LV dilatation, dysfunction, and hypotension as well as by increased BNP gene expression. By comparing LV-CHF vs. LV-CTRL, proteins were found to be underexpressed at 3 crucial points of cellular energy metabolism. In RV-CHF vs. RV-CTRL, proteins belonging to respiratory chain complexes were underexpressed, but additionally a disturbance in the nitric oxide-generating enzymatic apparatus was seen. Regarding the interventricular analyses, a stronger expression of energetic pathways was accompanied by an underexpression of contractile and stress response proteins in failing left vs. right ventricles. Finally, significant protein expression differences were found in LV-CTRL vs. RV-CTRL reflecting a higher expression of contractile, stress response, and respiratory chain proteins in LV tissue. CONCLUSIONS: In tachycardia-induced heart failure, significant inter- and intraventricular protein expression patterns were found with a predominance of proteins, which are involved in cellular energy metabolism.
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