Birner Christoph, Hierl Sarah, Dietl Alexander, Hupf Julian, Jungbauer Carsten, Schmid Peter M, Rümmele Petra, Deutzmann Rainer, Riegger Günter, Luchner Andreas
Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
Cell Physiol Biochem. 2014;33(3):692-704. doi: 10.1159/000358645. Epub 2014 Mar 7.
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.
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.
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
Experimental heart failure profoundly alters the pulmonary proteome. Our results supplement the current knowledge of pulmonary stress failure by specifying its molecular fundament.
心力衰竭（CHF）的特征为呼吸困难和肺部改变。其潜在的分子适应性尚不清楚，但可能为治疗干预提供靶点。因此，我们设计了一项研究，以确定在心动过速诱发的心力衰竭模型中早期肺应激衰竭的分子变化。
通过逐步右心室起搏诱导兔发生CHF（n = 6）。反复进行有创血压测量和超声心动图检查。未治疗的动物作为对照（n = 6）。对肺组织标本进行二维凝胶电泳，并通过质谱鉴定差异表达的蛋白质。通过蛋白质印迹分析验证选定的蛋白质，并通过免疫组织化学染色进行定位。
CHF动物的功能、形态和血流动力学参数发生了显著改变。通过蛋白质组学分析，共发现33种蛋白质在CHF动物的肺组织中差异表达（18种上调，15种下调），属于4个功能组：1. 参与维持细胞结构完整性的蛋白质；2. 表明肺泡-毛细血管通透性受损的血浆蛋白质；3. 具有抗氧化特性的蛋白质；4. 参与硒化合物代谢的蛋白质。
实验性心力衰竭深刻改变了肺蛋白质组。我们的结果通过明确其分子基础，补充了目前关于肺应激衰竭的知识。
