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扩张型心肌病合并心力衰竭患者血浆外泌体 microRNAs 的差异表达谱。

Differential expression profiles of plasma exosomal microRNAs in dilated cardiomyopathy with chronic heart failure.

机构信息

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, China.

出版信息

J Cell Mol Med. 2023 Jul;27(14):1988-2003. doi: 10.1111/jcmm.17789. Epub 2023 May 27.

Abstract

As one of the most prevalent heritable cardiovascular diseases, dilated cardiomyopathy (DCM) induces cardiac insufficiency and dysfunction. Although genetic mutation has been identified one of the causes of DCM, the usage of genetic biomarkers such as RNAs for DCM early diagnosis is still being overlooked. In addition, the alternation of RNAs could reflect the progression of the diseases, as an indicator for the prognosis of patients. Therefore, it is beneficial to develop genetic based diagnostic tool for DCM. RNAs are often unstable within circulatory system, leading to the infeasibility for clinical application. Recently discovered exosomal miRNAs have the stability that is then need for diagnostic purpose. Hence, fully understanding of the exosomal miRNA within DCM patients is vital for clinical translation. In this study, we employed the next generation sequencing based on the plasma exosomal miRNAs to comprehensively characterize the miRNAs expression in plasma exosomes from DCM patients exhibiting chronic heart failure (CHF) compared to healthy individuals. A complex landscape of differential miRNAs and target genes in DCM with CHF patients were identified. More importantly, we discovered that 92 differentially expressed miRNAs in DCM patients undergoing CHF were correlated with several enriched pathways, including oxytocin signalling pathway, circadian entrainment, hippo signalling pathway-multiple species, ras signalling pathway and morphine addiction. This study reveals the miRNA expression profiles in plasma exosomes in DCM patients with CHF, and further reveal their potential roles in the pathogenesis of it, presenting a new direction for clinical diagnosis and management of DCM patients with CHF.

摘要

作为最常见的遗传性心血管疾病之一,扩张型心肌病(DCM)可导致心脏功能不全和功能障碍。虽然基因突变已被确定为 DCM 的原因之一,但人们仍然忽视了使用 RNA 等遗传生物标志物进行 DCM 早期诊断。此外,RNA 的变化可以反映疾病的进展,作为患者预后的指标。因此,开发基于遗传的 DCM 诊断工具是有益的。RNA 在循环系统中通常不稳定,因此不适合临床应用。最近发现的外泌体 miRNAs 具有用于诊断目的的稳定性。因此,充分了解 DCM 患者中的外泌体 miRNA 对于临床转化至关重要。在这项研究中,我们采用了基于血浆外泌体 miRNAs 的下一代测序技术,全面描述了与健康个体相比,患有慢性心力衰竭(CHF)的 DCM 患者血浆外泌体中 miRNAs 的表达情况。确定了 DCM 合并 CHF 患者中差异表达 miRNA 和靶基因的复杂图谱。更重要的是,我们发现 92 个在 DCM 患者中差异表达的 miRNA 与几个富集途径有关,包括催产素信号通路、昼夜节律调节、 Hippo 信号通路-多物种、ras 信号通路和吗啡成瘾。这项研究揭示了 DCM 合并 CHF 患者血浆外泌体中的 miRNA 表达谱,并进一步揭示了它们在发病机制中的潜在作用,为 DCM 合并 CHF 患者的临床诊断和管理提供了新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ac/10339102/bbf3e57dae49/JCMM-27-1988-g004.jpg

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