Early ischemia-reperfusion in male mouse left ventricle nuclei induced marked proteome remodelling, with >250 proteins increased and ~30 decreased versus sham.
High-sensitivity mass spectrometry-based proteomics revealed significant early nuclear proteome remodeling in the male left ventricle following ischemia-reperfusion injury, providing a framework for identifying cardioprotective targets.
Abstract Background Early events following myocardial ischemia–reperfusion (I/R) represent a critical therapeutic window. Nuclear reprogramming is central to cellular phenotype and tissue homeostasis, yet remodelling of the cardiac nuclei during this phase is poorly understood. Purpose To generate a chamber-resolved cardiac nuclear proteome for the characterisation of early remodelling after I/R. This will enable resolution of molecular targets at a subcellular and regional level for cardiac repair. Methods We optimised a chamber-specific nuclear-enrichment proteomics workflow for the heart. In the I/R model, C57BL/6 mice underwent transient coronary ligation followed by 4 h reperfusion or sham surgery. Cardiac tissues were subjected to subcellular fractionation followed by high-sensitivity mass spectrometry-based proteomics. Nuclear enrichment and regional localisation of selected proteins were validated on heart by immunofluorescence microscopy. Results We defined a novel nuclear proteome signature of the heart and its regions. In sham hearts, we resolved 2,876 nuclear-enriched protein groups across cardiac chambers, defining region-resolved nuclear signatures enriched for RNA processing, chromatin regulation, nuclear envelope/lamina, proteostasis, stress-response and cell-death-related programs. Importantly, male left ventricle (LV) nuclei, early (4 h) I/R induced marked proteome remodelling, with 250 proteins increased and ~30 decreased versus sham with limited remodelling in corresponding female group. Differentially expressed proteins included stress-responsive transcriptional regulators, DNA-damage and chromatin-associated factors, RNA-regulatory proteins, and nucleo–cytoskeletal components with reported nuclear or perinuclear roles, consistent with rapid activation of nuclear stress-response and remodelling pathways in the reperfused LV. Conclusion This optimised nuclear-enrichment and proteomic workflow enabled a high-coverage, chamber-resolved mapping of the cardiac nuclear proteome and revealed selective early remodelling of the LV nuclear landscape after IR. These insights provide a framework for linking nuclear proteomic changes to injury and will prioritise candidate pathways for cardioprotective intervention within the acute reperfusion window.Graphical abstractFor image description, please refer to the figure legend and surrounding text.
Eslami et al. (Fri,) conducted a other in Myocardial ischemia-reperfusion. Transient coronary ligation (ischemia-reperfusion) vs. Sham surgery was evaluated on Nuclear proteome remodelling. Early ischemia-reperfusion in male mouse left ventricle nuclei induced marked proteome remodelling, with >250 proteins increased and ~30 decreased versus sham.