Transcriptome analysis reveals distinct patterns of long noncoding RNAs in heart and plasma of mice with heart failure

PLoS One. 2013 Oct 29;8(10):e77938. doi: 10.1371/journal.pone.0077938. eCollection 2013.


Objective: To 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.

Methods: Here 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.

Results: We 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.

Conclusions: We 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Cardiotonic Agents / toxicity
  • Gene Expression Profiling*
  • Heart Failure / chemically induced
  • Heart Failure / genetics*
  • Heart Failure / metabolism
  • Isoproterenol / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / blood*
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers
  • Cardiotonic Agents
  • RNA, Long Noncoding
  • RNA, Messenger
  • Isoproterenol

Grants and funding

This study was supported by the Major State Basic Research Development Program of China (Nos. 2012CB517806, 2012CB5106 and 2009CB941603), the National Natural Science Foundation of China (81170235 and 81070114), and the Program for New Century Excellent Talents in University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.