Abstract
ObjectiveTo assess the global changes in and characteristics of the transcriptome of long noncoding RNAs (LncRNAs) in heart tissue, whole blood and plasma during heart failure (HF) and association with expression of paired coding genes.MethodsHere we used microarray assay to examine the transcriptome of LncRNAs deregulated in the heart, whole blood, and plasma during HF in mice. We confirmed the changes in LncRNAs by quantitative PCR.ResultsWe revealed and confirmed a number of LncRNAs that were deregulated during HF, which suggests a potential role of LncRNAs in HF. Strikingly, the patterns of expression of LncRNA differed between plasma and other tissue during HF. LncRNA expression was associated with LncRNA length in all samples but not in plasma during HF, which suggests that the global association of LncRNA expression and LncRNA length in plasma could be biomarkers for HF. In total, 32 LncRNAs all expressed in the heart, whole blood and plasma showed changed expression with HF, so they may be biomarkers in HF. In addition, sense-overlapped LncRNAs tended to show consistent expression with their paired coding genes, whereas antisense-overlapped LncRNAs tended to show the opposite expression in plasma; so different types of LncRNAs may have different characteristics in HF. Interestingly, we revealed an inverse correlation between changes in expression of LncRNAs in plasma and in heart, so circulating levels of LncRNAs may not represent just passive leakage from the HF heart but also active regulation or release of circulatory cells or other cells during HF.ConclusionsWe reveal stable expression of LncRNAs in plasma during HF, which suggests a newly described component in plasma. The distinct expression patterns of circulatory LncRNAs during HF indicate that LncRNAs may actively respond to stress and thus serve as biomarkers of HF diagnosis and treatment.
Highlights
In analyses of the human transcriptome, most transcripts have little or no protein-coding capacity but rather are noncoding RNAs [1], which adds novel content to traditional protein-centric molecular biology [2]
We confirmed the isoproterenol-induced heart failure (HF) in mice as elevated mRNA level of brain natriuretic protein, local necrosis in endocardium, hyperplasia of fibroblasts (Fig. 1C and D), and impaired cardiac pump function evidenced by lowered LV6dp/dtmax and increased left ventricular end diastolic pressure (LVEDP) (Table 1, P,0.01)
In this acute HF model, we found 518 long noncoding RNAs (LncRNAs) upregulated and 908 downregulated (Table S2) by high-output microarray analysis
Summary
In analyses of the human transcriptome, most transcripts have little or no protein-coding capacity but rather are noncoding RNAs [1], which adds novel content to traditional protein-centric molecular biology [2]. MicroRNAs (miRNAs), a class of small noncoding RNAs, are critical in biology and medicine [3]. When LncRNAs were discovered, they were considered not to have important function [5] because of their low conservation, low expression level and high tissue specificity [5,6,7]. A number of LncRNAs have been found to have important and diverse functions [8,9]. LncRNA-related dysfunction has been found to play critical roles in various diseases [10,11], including cancers [12], cardiovascular diseases [2], and neurodegeneration diseases [13]. LncRNAs are becoming important biological molecules for understanding the mechanisms of disease and for exploring biomarkers for disease diagnosis and treatment
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