Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Cardiac Electrophysiology and Arrhythmia, Shandong First Medical University, Jinan, China.
Medical Integration and Practice Center, Shandong University, Jinan, China.
J Cell Mol Med. 2024 Aug;28(15):e18582. doi: 10.1111/jcmm.18582.
Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long-term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long-term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high-throughput sequencing and TMT-tagged LC-MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long-term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long-term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.
导管消融（CA）是治疗心房颤动（AF）的介入治疗的重要方法，降低 CA 后的长期复发非常重要。CA 后复发的机制仍不清楚。我们建立了环肺静脉消融（CPVA）后比格犬的长期模型。使用高通量测序和 TMT 标记 LC-MS/LC 分析分别获得转录组和蛋白质组。筛选和富集差异表达的基因和蛋白质，并在组织中发现和验证纤维化的影响。下调的蛋白，神经肽 Y（NPY），被选择进行验证，结果表明 NPY 可能在 CPVA 后 AF 的长期再诱导中发挥作用。然后，进一步研究了 NPY 的分子机制。结果表明，CPVA 后心房有效不应期（AERP）缩短，纤维化增加。NPY 干预减轻了心房肌细胞凋亡，抑制了心肌成纤维细胞中 Akt 的激活。这些结果表明，CPVA 后长期抑制 NPY 可能通过促进心肌细胞凋亡和激活心肌成纤维细胞中的 Akt 途径导致 AF 的再诱导，这可能使 AF 更容易再诱导。
