Experimental Heart Failure Induces Alterations of the Lung Proteome - Insight into Molecular Mechanisms

• Main Authors: Christoph Birner, Sarah Hierl, Alexander Dietl, Julian Hupf, Carsten Jungbauer, Peter M. Schmid, Petra Rümmele, Rainer Deutzmann, Günter Riegger, Andreas Luchner
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2014-03-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Proteomics; Lung; Experimental heart failure
• Online Access: http://www.karger.com/Article/FullText/358645

Background: Heart failure (CHF) is characterized by dyspnea and pulmonary changes. The underlying molecular adaptations are unclear, but might provide targets for therapeutic interventions. We therefore conceived a study to determine molecular changes of early pulmonary stress failure in a model of tachycardia-induced heart failure. Methods: CHF was induced in rabbits by progessive right ventricular pacing (n=6). Invasive blood pressure measurements and echocardiography were repeatedly performed. Untreated animals served as controls (n=6). Pulmonary tissue specimens were subjected to two-dimensional gel electrophoresis, and differentially expressed proteins were identified by mass spectrometry. Selected proteins were validated by Western Blot analysis and localized by immunohistochemical staining. Results: CHF animals were characterized by significantly altered functional, morphological, and hemodynamic parameters. Upon proteomic profiling, a total of 33 proteins was found to be differentially expressed in pulmonary tissue of CHF animals (18 up-regulated, and 15 down-regulated) belonging to 4 functional groups: 1. proteins involved in maintaining cytoarchitectural integrity, 2. plasma proteins indicating impaired alveolar-capillary permeability, 3. proteins with antioxidative properties, and 4. proteins participating in the metabolism of selenium compounds Conclusion: Experimental heart failure profoundly alters the pulmonary proteome. Our results supplement the current knowledge of pulmonary stress failure by specifying its molecular fundament.