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心肌活检犬扩张型心肌病表型的基因表达谱分析。

Gene-expression profiling of endomyocardial biopsies from dogs with dilated cardiomyopathy phenotype.

机构信息

Department of Veterinary Medicine and Animal Productions, University Federico II, Napoli, 80130, Italy.

Department of Veterinary Medicine and Animal Productions, University Federico II, Napoli, 80130, Italy; Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, 84081, Baronissi, SA, Italy; Medical Genomics Program, AOU 'SS. Giovanni di Dio e Ruggi d'Aragona', University of Salerno, 84131 Salerno, Italy.

出版信息

J Vet Cardiol. 2024 Apr;52:78-89. doi: 10.1016/j.jvc.2024.02.008. Epub 2024 Feb 22.

DOI:10.1016/j.jvc.2024.02.008
PMID:38508121
Abstract

INTRODUCTION

The employment of advanced molecular biology technologies has expanded the diagnostic investigation of cardiomyopathies in dogs; these technologies have predominantly been performed on postmortem samples, although the recent use of endomyocardial biopsy in living dogs has enabled a better premortem diagnostic approach to study the myocardial injury.

ANIMALS, MATERIALS, AND METHODS: Endomyocardial biopsies were collected in nine dogs with a dilated cardiomyopathy phenotype (DCM-p) and congestive heart failure and submitted to histologic examination, next-generation sequencing (NGS), and polymerase chain reaction analysis. Data from three healthy dogs (Fastq files) were retrieved from a previously approved study and used as a control group for ribonucleic acid sequencing.

RESULTS

Histologic examination revealed endocardial fibrosis in six of nine dogs, whereas lymphocytic interstitial infiltrates were detected in two of nine dogs, and lymphoplasmacytic and macrophage infiltrates were detected in one of nine dogs. On polymerase chain reaction analysis, two dogs tested positive for canine parvovirus two and one dog for canine distemper virus. Gene-expression pathways involved in cellular energy metabolism (especially carbohydrates-insulin) and cardiac structural proteins were different in all DCM-p dogs compared to those in the control group. When dogs with lymphocytic interstitial infiltrates were compared to those in the control group, NGS analysis revealed the predominant role of genes related to inflammation and pathogen infection.

CONCLUSIONS

Next-generation sequencing technology performed on in vivo endomyocardial biopsies has identified different molecular and genetic factors that could play a role in the development and/or progression of DCM-p in dogs.

摘要

简介

先进的分子生物学技术的应用扩大了犬心肌病的诊断研究范围;这些技术主要在死后样本上进行,尽管最近在活犬中使用心内膜心肌活检使人们能够更好地进行生前诊断,以研究心肌损伤。

动物、材料和方法:采集了 9 只具有扩张型心肌病表型(DCM-p)和充血性心力衰竭的犬的心内膜心肌活检标本,并进行组织学检查、下一代测序(NGS)和聚合酶链反应分析。从之前批准的一项研究中检索了 3 只健康犬的数据(Fastq 文件),并将其用作核糖核酸测序的对照组。

结果

组织学检查显示 6 只犬的心内膜纤维化,9 只犬中有 2 只犬的间质淋巴细胞浸润,9 只犬中有 1 只犬的淋巴浆细胞和巨噬细胞浸润。聚合酶链反应分析显示,2 只犬的犬细小病毒 2 型检测呈阳性,1 只犬的犬瘟热病毒检测呈阳性。与对照组相比,所有 DCM-p 犬的细胞能量代谢(尤其是碳水化合物-胰岛素)和心脏结构蛋白相关的基因表达途径均不同。与对照组相比,具有间质性淋巴细胞浸润的犬的 NGS 分析显示,与炎症和病原体感染相关的基因起主要作用。

结论

在体内心内膜心肌活检上进行的下一代测序技术已经确定了不同的分子和遗传因素,这些因素可能在犬 DCM-p 的发展和/或进展中起作用。

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