Long-term impact of CVB3-induced miRNA dysregulation on cardiac function using small RNA sequencing in CVB3-infected mice with myocarditis and human dilated cardiomyopathy hearts

CVB3 is a major cause of viral myocarditis in humans, an inflammatory disease that can progress to chronic myocarditis or dilated cardiomyopathy (DCM). Immune responses during myocarditis significantly impact DCM development and progression. Genetic variations can affect these responses, causing prolonged cytotoxicity, host protein cleavage, and abnormal wound healing, leading to tissue scarring and impaired heart function. The specific immune changes and molecular mechanisms in myocarditis remain unclear. miRNAs are implicated in CVB3-induced myocarditis, but their role in disease progression is not well-studied. We aimed to understand the long-term impact of CVB3-induced miRNA dysregulation on cardiac function. Using small RNA sequencing, we analyzed hearts from CVB3-infected mice with myocarditis. Due to the unavailability of CVB3-infected human samples, we used human DCM hearts of unknown etiology, discarded post-transplants, as a model of long-term cardiac pathogenesis. Our goal was to identify differentially expressed genes (DEGs) regulated by miRNAs involved in the progression from myocarditis to DCM. This integration of mouse and human data provides a foundation for understanding the molecular mechanisms in CVB3-induced myocarditis and DCM.

柯萨奇病毒B3（CVB3）是人类病毒性心肌炎的主要致病原，病毒性心肌炎是一类可进展为慢性心肌炎或扩张型心肌病（dilated cardiomyopathy, DCM）的炎症性疾病。心肌炎发生过程中的免疫应答可显著影响DCM的发生与进展。遗传变异可调控此类免疫应答，引发持续性细胞毒性、宿主蛋白裂解及异常伤口愈合，最终导致组织瘢痕形成与心脏功能受损。目前针对心肌炎中特异性免疫变化与分子机制的研究仍不明确。微小RNA（miRNAs）已被证实与CVB3诱导的心肌炎相关，但其在疾病进展中的作用尚未得到充分研究。本研究旨在探究CVB3诱导的miRNAs表达失调对心脏功能的长期影响。本研究通过小RNA测序技术，对感染CVB3并诱发心肌炎的小鼠心脏样本进行了分析。由于无法获取CVB3感染的人类样本，本研究采用病因不明的移植术后废弃人类DCM心脏组织作为长期心脏发病机制的研究模型。本研究的目标是筛选出由参与心肌炎向DCM进展过程的miRNAs所调控的差异表达基因（differentially expressed genes, DEGs）。本研究整合小鼠与人类样本数据，为阐明CVB3诱导的心肌炎及DCM的分子机制奠定了研究基础。