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扩张型心肌病伴心力衰竭患者血浆外泌体中circRNA的差异表达谱

Differential Expression Spectrum of circRNA in Plasma Exosomes in Dilated Cardiomyopathy With Heart Failure.

作者信息

Xu Shuai, Zhang Ge, Tan Xin, Zeng Yiyao, Fan Huimin, Gao Jiamin, Qin Zhen, Yu Fengyi, Ma Bin, Zhang Ting, Jiang Hezi, Li Xian, Wang Xiangyu, Fan Jili, Bo Xiaohong, Zhou Yafeng, Tang Junnan

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. 2024 Dec;28(24):e70258. doi: 10.1111/jcmm.70258.

Abstract

Dilated cardiomyopathy (DCM), a form of non-ischaemic myocardial disease, is characterised by structural and functional cardiac abnormalities. As defined by the World Health Organisation, DCM constitutes a significant cardiac pathology, leading to increased morbidity and mortality due to complications such as heart failure and arrhythmias. The diagnostic process for DCM predominantly employs echocardiography and MRI, with biomarkers like NT-pro BNP and troponin providing supportive, yet non-specific, evidence. Exosomes, small extracellular vesicles, play a critical role in intercellular communications by transferring biomolecules including lipids, proteins, messenger RNA (mRNA) and non-coding RNA (ncRNA) to target cells, thereby influencing key cellular processes such as proliferation, differentiation, apoptosis, angiogenesis and immune modulation. Within the ncRNA category, circular RNAs (circRNAs) are notable for their cellular specificity and evolutionary conservation and are often implicated in the regulatory mechanisms underlying DCM and heart failure. This investigation employed next-generation sequencing technology to analyse plasma exosomal circRNA profiles in DCM patients with chronic heart failure (CHF), compared to healthy controls. The analysis revealed distinct circRNA expression patterns, identifying 49 uniquely expressed circRNAs in the DCM cohort with CHF. These circRNAs were associated with several critical biological pathways, including the sequestration of extracellular ligands from receptors, N-acetyltransferase activity, histone acetyltransferase activity and endocytic vesicle membrane composition. The findings of this study provide valuable insights into the pathophysiological mechanisms of DCM and offer evidence for improving clinical diagnostic methodologies.

摘要

扩张型心肌病(DCM)是一种非缺血性心肌病,其特征为心脏结构和功能异常。根据世界卫生组织的定义,DCM是一种重要的心脏病理学疾病,由于心力衰竭和心律失常等并发症,导致发病率和死亡率增加。DCM的诊断过程主要采用超声心动图和磁共振成像,生物标志物如N末端B型利钠肽原(NT-pro BNP)和肌钙蛋白提供支持性但非特异性的证据。外泌体是小细胞外囊泡,通过将包括脂质、蛋白质、信使核糖核酸(mRNA)和非编码核糖核酸(ncRNA)在内的生物分子转移到靶细胞,在细胞间通讯中发挥关键作用,从而影响细胞增殖、分化、凋亡、血管生成和免疫调节等关键细胞过程。在ncRNA类别中,环状RNA(circRNA)因其细胞特异性和进化保守性而引人注目,并且常常与DCM和心力衰竭的潜在调控机制有关。本研究采用下一代测序技术,分析慢性心力衰竭(CHF)的DCM患者与健康对照者血浆外泌体circRNA谱。分析揭示了不同的circRNA表达模式,在伴有CHF的DCM队列中鉴定出49种独特表达的circRNA。这些circRNA与几种关键的生物学途径相关,包括从受体中隔离细胞外配体、N-乙酰转移酶活性、组蛋白乙酰转移酶活性和内吞囊泡膜组成。本研究结果为DCM的病理生理机制提供了有价值的见解,并为改进临床诊断方法提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0eaa/11668728/ae82345ce730/JCMM-28-e70258-g002.jpg

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