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PNAS:miRNA或成为心脏损伤全新标志物
人阅读 发布时间:2014-08-07 10:00
7月29日发布的PNAS杂志中,美国洛克菲勒大学和哥伦比亚大学研究者撰文发布了他们关于miRNA同心力衰竭病人的心肌细胞之间联系的最新研究成果。
研究者利用small RNA-Seq技术,检测了大量不同时期心衰病人心肌细胞及血液系统中miRNA表达变化,并发现在心衰病人的血液中,有三个心脏组织特异的miRNA出现了显著上调。通过比较这三个显著上调的miRNA与心肌肌钙蛋白(cardiac troponin I protein, cTnI)的水平,证明二者存在很强的一致性。cTnI存在于正常心肌细胞中,当心肌组织受到损伤时,该蛋白会被泄漏进入血液,所以常作为标志物用于诊断心脏损伤。相比起cTnI,细胞内含有的miRNA复合物更容易释放到血液中,比如这三个心脏组织特异的miRNA。这就令miRNA可以成为一种更为通用和灵敏的心脏损伤诊断与治疗标志物。
本研究中,small RNA-Seq技术体现了高灵敏度、高通量等显著的技术优势,成为研究miRNA重要的技术手段。作为国内最强miRNA研究者,锐博生物利用核心专利独立研发出了完整的miRNA类产品,包括miRNA mimic/inhibitor,miRNA agomir/antagomir,miRNA qPCR等,同时拥有最先进技术服务平台,提供small RNA-Seq、mRNA-Seq、RIP-Seq、CLIP-Seq、高内涵筛选及小动物活体成像等服务项目,从上游发现差异到下游功能验证,为研究者定制最全面研究策略,是您最佳研究伙伴!
锐博生物推荐原文摘要
Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers
Heart failure (HF) is associated with high morbidity and mortality and its incidence is increasing worldwide. MicroRNAs (miRNAs) are potential markers and targets for diagnostic and therapeutic applications, respectively. We determined myocardial and circulating miRNA abundance and its changes in patients with stable and end-stage HF before and at different time points after mechanical unloading by a left ventricular assist device (LVAD) by small RNA sequencing. miRNA changes in failing heart tissues partially resembled that of fetal myocardium. Consistent with prototypical miRNA–target-mRNA interactions, target mRNA levels were negatively correlated with changes in abundance for highly expressed miRNAs in HF and fetal hearts. The circulating small RNA profile was dominated by miRNAs, and fragments of tRNAs and small cytoplasmic RNAs. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced HF, which coincided with a similar increase in cardiac troponin I (cTnI) protein, the established marker for heart injury. These extracellular changes nearly completely reversed 3 mo following initiation of LVAD support. In stable HF, circulating miRNAs showed less than fivefold differences compared with normal, and myomir and cTnI levels were only captured near the detection limit. These findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury performing similar to established diagnostic protein biomarkers.