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症状性猫肥厚型心肌病和健康对照猫的凝血和蛋白质组学特征研究。

Investigation of coagulation and proteomics profiles in symptomatic feline hypertrophic cardiomyopathy and healthy control cats.

机构信息

Graduate School, Veterinary Clinical Studies Program, Faculty of Veterinary Medicine, Kasetsart University, Kamphaeng Saen, Nakorn Pathom, Thailand.

Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand.

出版信息

BMC Vet Res. 2024 Jul 5;20(1):292. doi: 10.1186/s12917-024-04170-0.

DOI:10.1186/s12917-024-04170-0
PMID:38970022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11225243/
Abstract

BACKGROUND

Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM.

RESULTS

Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway.

CONCLUSIONS

Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.

摘要

背景

肥厚型心肌病(HCM)是猫的一种重要心脏病。HCM 的临床表现包括肺水肿、呼吸困难、晕厥、动脉血栓栓塞(ATE)和心源性猝死。D-二聚体和凝血酶原时间(PT)是用于评估凝血功能的有力生物标志物。这两种生物标志物的失调可能与猫的 HCM 有关。本研究旨在评估健康猫与有症状 HCM 猫的 D-二聚体水平、PT 和蛋白质组谱。

结果

共纳入 29 只患有 HCM 的患宠猫,包括 15 只健康对照猫和 14 只有症状 HCM 猫。检测了 D-二聚体浓度和 PT。通过基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱和液相色谱-串联质谱(LC-MS/MS)进行蛋白质组分析。在有症状的猫中,D-二聚体水平明显高于健康猫(均值±SEM:372.19ng/ml±58.28),差异有统计学意义(P<0.01),而有症状的猫的 PT 明显低于健康猫(均值±SEM:9.8s±0.15),差异有统计学意义(P<0.0001)。蛋白质组学分析显示,整合素亚基α M(ITGAM)、伸长蛋白 B(ELOB)和原纤维蛋白 2(FBN2)上调,锌指蛋白 316(ZNF316)和核苷酸三磷酸二磷酸水解酶 8(ENTPD8)下调。此外,蛋白质-药物相互作用分析鉴定了 Ras 信号通路和 PI3K-Akt 信号通路。

结论

有症状 HCM 猫的 D-二聚体较高,PT 较低。蛋白质组谱可能作为检测和管理猫 HCM 的潜在生物标志物。在猫中,D-二聚体作为 HCM 检测的生物标志物,以及蛋白质组谱分析用于更好地了解疾病机制,仍有待进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/167b/11225243/09ebc4ae9006/12917_2024_4170_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/167b/11225243/f51358293d23/12917_2024_4170_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/167b/11225243/f51358293d23/12917_2024_4170_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/167b/11225243/f6161488cd0c/12917_2024_4170_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/167b/11225243/2dc38e714131/12917_2024_4170_Fig3_HTML.jpg
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