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原发性心肌病导致充血性心力衰竭的猫的新型生物标志物。

Novel biomarkers in cats with congestive heart failure due to primary cardiomyopathy.

机构信息

Small Animal Hospital, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK; Laboratory for Proteomics, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia.

出版信息

J Proteomics. 2020 Aug 30;226:103896. doi: 10.1016/j.jprot.2020.103896. Epub 2020 Jul 9.

DOI:10.1016/j.jprot.2020.103896
PMID:32652222
Abstract

The pathogenesis of feline cardiomyopathy and congestive heart failure (CHF) requires further understanding. In this study, we assessed serum proteome change in feline CHF, aiming to identify novel biomarker for both research and clinical use. The study comprised 15 cats in CHF, 5 cats in preclinical cardiomyopathy and 15 cats as healthy controls. Serum proteome profiles were obtained by tandem mass tag labelling followed by mass spectrometry. Protein concentrations in CHF cats were compared with healthy controls. Western blot was performed for proteomic validation. Correlations were assessed between the altered proteins in CHF and clinical variables in cats with cardiomyopathy to evaluate protein-cardiac association. Bioinformatic analysis was employed to identify pathophysiological pathways involved in feline CHF. Sixteen serum proteins were significantly different between CHF and healthy control cats (P < .05). These included serine protease inhibitors, apolipoproteins and other proteins associated with inflammation and coagulation. Clinical parameters from cats with cardiomyopathy significantly correlated with the altered proteins (P < .05). Bioinformatic analysis identified 13 most relevant functional profiles in feline CHF, which mostly associated with extracellular matrix organization and metabolism. Data are available via ProteomeXchange with identifier PXD017761. SIGNIFICANCE: Cardiomyopathies affect both cats and humans, and they can cause serious consequence such as congestive heart failure (CHF). To date, the pathophysiological mechanism of CHF is not fully understood. In this study, for the first time, we used a proteomic approach combined with bioinformatic analysis to evaluate serum protein change in cats with CHF. Results indicate systemic inflammation, coagulation protein changes, innate immunity and extracellular matrix remodeling are involved in feline CHF, which are largely comparable with findings in previous human studies. Our study provides new insights into CHF and cardiomyopathy in cats, and the identified novel biomarkers and pathophysiological pathways provide valuable information for future studies.

摘要

猫扩张型心肌病和充血性心力衰竭(CHF)的发病机制需要进一步了解。在这项研究中,我们评估了猫 CHF 的血清蛋白质组变化,旨在为研究和临床应用鉴定新的生物标志物。该研究包括 15 只 CHF 猫、5 只临床前期心肌病猫和 15 只健康对照猫。采用串联质量标签标记和质谱法获得血清蛋白质组谱。比较 CHF 猫与健康对照猫的血清蛋白浓度。进行蛋白质印迹以进行蛋白质组学验证。评估 CHF 中改变的蛋白质与患有心肌病的猫的临床变量之间的相关性,以评估蛋白质-心脏相关性。使用生物信息学分析鉴定涉及猫 CHF 的病理生理途径。CHF 猫与健康对照猫之间有 16 种血清蛋白差异显著(P<.05)。这些包括丝氨酸蛋白酶抑制剂、载脂蛋白和其他与炎症和凝血相关的蛋白质。患有心肌病的猫的临床参数与改变的蛋白质显著相关(P<.05)。生物信息学分析确定了猫 CHF 中 13 个最相关的功能谱,这些功能谱主要与细胞外基质组织和代谢有关。数据可通过 ProteomeXchange 获得,标识符为 PXD017761。意义:心肌病影响猫和人类,可导致充血性心力衰竭(CHF)等严重后果。迄今为止,CHF 的病理生理机制尚未完全了解。在这项研究中,我们首次使用蛋白质组学方法结合生物信息学分析来评估 CHF 猫的血清蛋白变化。结果表明,全身性炎症、凝血蛋白变化、先天免疫和细胞外基质重塑参与了猫的 CHF,这与以前的人类研究结果大致相当。我们的研究为猫的 CHF 和心肌病提供了新的见解,所鉴定的新型生物标志物和病理生理途径为未来的研究提供了有价值的信息。

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