The diaphragm is the main inspiratory muscle, and the chronic phase post-myocardial infarction (MI) is characterized by diaphragm morphological, contractile, and metabolic abnormalities. However, the mechanisms of diaphragm weakness are not fully understood. In the current study, we aimed to identify the transcriptome changes associated with diaphragm abnormalities in the chronic stage MI. We ligated the left coronary artery to cause MI in rats and performed RNA-sequencing (RNA-Seq) in diaphragm samples 16 weeks post-surgery. The sham group underwent thoracotomy and pericardiotomy but no artery ligation. We identified 112 differentially expressed genes (DEGs) out of a total of 9664 genes. Myocardial infarction upregulated and downregulated 42 and 70 genes, respectively. Analysis of DEGs in the framework of skeletal muscle-specific biological networks suggest remodeling in the neuromuscular junction, extracellular matrix, sarcomere, cytoskeleton, and changes in metabolism and iron homeostasis. Overall, the data are consistent with pathological remodeling of the diaphragm and reveal potential biological targets to prevent diaphragm weakness in the chronic stage MI.

膈肌是主要的吸气肌，心肌梗死后慢性期以膈肌形态、收缩和代谢异常为特征。然而，膈肌无力的机制尚不完全清楚。在当前的研究中，我们旨在确定与慢性 MI 中的横膈膜异常相关的转录组变化。我们结扎左冠状动脉以引起大鼠 MI，并在术后 16 周对隔膜样本进行 RNA 测序 (RNA-Seq)。假手术组接受开胸术和心包切开术但不结扎动脉。我们从总共 9664 个基因中鉴定出 112 个差异表达基因 (DEG)。心肌梗死分别上调和下调了 42 和 70 个基因。在骨骼肌特异性生物网络框架内对 DEG 的分析表明，神经肌肉接头、细胞外基质、肌节、细胞骨架发生重塑，以及新陈代谢和铁稳态发生变化。总体而言，这些数据与横膈膜的病理重塑一致，并揭示了预防慢性 MI 中横膈膜无力的潜在生物学靶点。