Wardman Rhys, Grein Steve, Schwartz Jennifer, Stein Frank, Heineke Joerg
Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
German Center for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany.
Sci Data. 2025 Aug 2;12(1):1347. doi: 10.1038/s41597-025-05506-7.
Transaortic constriction (TAC) is a murine model of pressure overload-induced cardiac hypertrophy and heart failure. Despite its high prevalence during aortic stenosis or chronic arterial hypertension, the global alterations in cardiac phospho-proteome dynamics following TAC remain incompletely characterised. We present a database of the phospho-proteomic signature one day and seven days after TAC. Utilising proteomic and phospho-proteomic analyses, we quantified thousands of proteins and phosphorylation sites, revealing hundreds of differential phosphorylation events significantly altered in the cardiac response to pressure overload. Our analysis highlights significant changes in hypertrophic signalling, metabolic remodelling, contractile function, and the stress response pathways. We present proteomic data from the main cardiac cell types (endothelial cells, fibroblasts and cardiomyocytes) to reveal the cellular localisation of the detected phospho-proteins, offering insights into temporal and site-specific phosphorylation events, facilitating the potential discovery of novel therapeutic targets and biomarkers. By making this resource publicly available (ProteomeXchange with identifier PXD061784) we aim to enable further exploration of the molecular basis of cardiac remodelling and advance translational research in heart failure.
经主动脉缩窄（TAC）是一种压力超负荷诱导的心肌肥大和心力衰竭的小鼠模型。尽管在主动脉瓣狭窄或慢性动脉高血压期间其发病率很高，但TAC后心脏磷酸化蛋白质组动力学的整体变化仍未完全明确。我们展示了TAC后一天和七天的磷酸化蛋白质组特征数据库。利用蛋白质组学和磷酸化蛋白质组学分析，我们对数千种蛋白质和磷酸化位点进行了定量，揭示了数百种在心脏对压力超负荷反应中显著改变的差异磷酸化事件。我们的分析突出了肥厚信号传导、代谢重塑、收缩功能和应激反应途径中的显著变化。我们展示了主要心脏细胞类型（内皮细胞、成纤维细胞和心肌细胞）的蛋白质组数据，以揭示检测到的磷酸化蛋白质的细胞定位，深入了解时间和位点特异性磷酸化事件，促进新型治疗靶点和生物标志物的潜在发现。通过公开提供此资源（标识符为PXD061784的蛋白质组交换库），我们旨在推动对心脏重塑分子基础的进一步探索，并推进心力衰竭的转化研究。
