Rüdebusch Julia, Benkner Alexander, Poesch Axel, Dörr Marcus, Völker Uwe, Grube Karina, Hammer Elke, Felix Stephan B
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
DZHK (German Centre for Cardiovascular Research, partner site Greifswald), Greifswald, Germany.
PLoS One. 2017 Oct 3;12(10):e0185915. doi: 10.1371/journal.pone.0185915. eCollection 2017.
Heart failure (HF) development is characterized by huge structural changes that are crucial for disease progression. Analysis of time dependent global proteomic adaptations during HF progression offers the potential to gain deeper insights in the disease development and identify new biomarker candidates. Therefore, hearts of TAC (transverse aortic constriction) and sham mice were examined by cardiac MRI on either day 4, 14, 21, 28, 42, and 56 after surgery (n = 6 per group/time point). At each time point, proteomes of the left (LV) and right ventricles (RV) of TAC and sham mice were analyzed by mass spectrometry (MS). In TAC mice, systolic LV heart function worsened from day 4 to day 14, remained on a stable level from day 14 to day 42, and showed a further pronounced decline at day 56. MS analysis identified in the LV 330 and in RV 246 proteins with altered abundance over time (TAC vs. sham, fc≥±2). Functional categorization of proteins disclosed the time-dependent alteration of different pathways. Heat shock protein beta-7 (HSPB7) displayed differences in abundance in tissue and serum at an early stage of HF. This study not only provides an overview of the time dependent molecular alterations during transition to HF, but also identified HSPB7 as a novel blood biomarker candidate for the onset of cardiac remodeling.
心力衰竭（HF）的发展以巨大的结构变化为特征，这些变化对疾病进展至关重要。分析HF进展过程中随时间变化的整体蛋白质组适应性，有可能更深入地了解疾病发展并识别新的生物标志物候选物。因此，在手术后第4、14、21、28、42和56天，通过心脏磁共振成像（MRI）检查主动脉缩窄（TAC）小鼠和假手术小鼠的心脏（每组/每个时间点n = 6）。在每个时间点，通过质谱（MS）分析TAC小鼠和假手术小鼠左心室（LV）和右心室（RV）的蛋白质组。在TAC小鼠中，LV收缩功能从第4天到第14天恶化，从第14天到第42天保持稳定水平，并在第56天进一步明显下降。MS分析在LV中鉴定出330种、在RV中鉴定出246种随着时间丰度发生改变的蛋白质（TAC与假手术相比，fc≥±2）。蛋白质的功能分类揭示了不同途径的时间依赖性改变。热休克蛋白β-7（HSPB7）在HF早期的组织和血清中丰度存在差异。本研究不仅提供了向HF转变过程中随时间变化的分子改变的概述，还将HSPB7鉴定为心脏重塑开始的新型血液生物标志物候选物。
