Department of Veterinary Medicine, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand, Bangkok, Thailand.
Center of Excellence for Companion Animal Cancer, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand, Bangkok, Thailand.
PeerJ. 2024 Apr 30;12:e17186. doi: 10.7717/peerj.17186. eCollection 2024.
Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Phosphorylation of proteins, impacting vascular function and cell proliferation, might play a role in the development and progression of PH. Unlike gene or protein studies, phosphoproteomic focuses on active proteins that function as end-target proteins within signaling cascades. Studying phosphorylated proteins can reveal active contributors to PH development. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach. Serum samples were collected from healthy control dogs ( = 28), dogs with DMVD ( = 24), and dogs with DMVD and PH ( = 29). Phosphoproteins were enriched from the serum samples and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data analysis was performed to identify uniquely expressed phosphoproteins in each group and differentially expressed phosphoproteins among groups. Phosphoproteomic analysis revealed nine uniquely expressed phosphoproteins in the serum of dogs in the DMVD+PH group and 15 differentially upregulated phosphoproteins in the DMVD+PH group compared to the DMVD group. The phosphoproteins previously implicated in PH and associated with pulmonary arterial remodeling, including small nuclear ribonucleoprotein G (SNRPG), alpha-2-macroglobulin (A2M), zinc finger and BTB domain containing 42 (ZBTB42), hemopexin (HPX), serotransferrin (TRF) and complement C3 (C3), were focused on. Their unique expression and differential upregulation in the serum of DMVD dogs with PH suggest their potential as biomarkers for PH diagnosis. In conclusion, this phosphoproteomic study identified uniquely expressed and differentially upregulated phosphoproteins in the serum of DMVD dogs with PH. Further studies are warranted to validate the diagnostic utility of these phosphoproteins.
肺动脉高压（PH）是一种常见的退行性二尖瓣疾病（DMVD）犬的并发症，是一种以肺动脉压（PAP）升高和肺血管重塑为特征的进行性疾病。蛋白质的磷酸化可能在 PH 的发展和进展中起作用，影响血管功能和细胞增殖。与基因或蛋白质研究不同，磷酸蛋白质组学专注于作为信号级联中的终靶蛋白起作用的活性蛋白。研究磷酸化蛋白质可以揭示 PH 发展的活跃贡献者。PH 的早期诊断对于有效的管理和改善临床结果至关重要。本研究旨在使用磷酸蛋白质组学方法鉴定诊断 DMVD 犬 PH 的潜在血清生物标志物。从健康对照犬（n = 28）、DMVD 犬（n = 24）和 DMVD 合并 PH 犬（n = 29）中采集血清样本。从血清样本中富集磷酸蛋白，并使用液相色谱-串联质谱（LC-MS/MS）进行分析。进行数据分析以鉴定每个组中唯一表达的磷酸蛋白和组间差异表达的磷酸蛋白。磷酸蛋白质组学分析显示，DMVD+PH 组血清中存在 9 种唯一表达的磷酸蛋白，与 DMVD 组相比，DMVD+PH 组中 15 种磷酸蛋白表达上调。先前与 PH 相关并与肺动脉重塑相关的磷酸蛋白，包括小核核糖核蛋白 G（SNRPG）、α-2-巨球蛋白（A2M）、锌指和 BTB 结构域包含 42（ZBTB42）、血红素结合蛋白（HPX）、转铁蛋白（TRF）和补体 C3（C3），受到关注。它们在 PH 犬 DMVD 血清中的独特表达和差异上调表明它们作为 PH 诊断标志物的潜力。总之，本磷酸蛋白质组学研究鉴定了 PH 犬 DMVD 血清中独特表达和差异上调的磷酸蛋白。需要进一步研究来验证这些磷酸蛋白的诊断效用。
