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Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs

Open access
Ounzain, S., Micheletti, R., Beckmann, T., Schroen, B., Alexanian, M., Pezzuto, I., Crippa, S., Nemir, M., Sarre, A., Johnson, R., Dauvillier, J., Burdet, F., Ibberson, M., Guigo, R., Xenarios, I., Heymans, S., Pedrazzini, T.·2015·European Heart Journal

Abstract

AIM: Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. METHODS AND RESULTS: We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. CONCLUSION: These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.

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Metadata

Authors
Ounzain, S., Micheletti, R., Beckmann, T., Schroen, B., Alexanian, M., Pezzuto, I., Crippa, S., Nemir, M., Sarre, A., Johnson, R., Dauvillier, J., Burdet, F., Ibberson, M., Guigo, R., Xenarios, I., Heymans, S., & Pedrazzini, T.
Venue
European Heart Journal
Published
2014-04-30
Volume
36
Issue
6
Pages
353-368
ISSN
  • 0195-668X (ISSN-L)
  • 1522-9645
OpenAlex
W2159612327
Cited by
281
References
13
FWCI
9.43
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs. https://app.cochat.ai/papers/10.1093/eurheartj/ehu180
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Ounzain, S., Micheletti, R., Beckmann, T., Schroen, B., Alexanian, M., Pezzuto, I., Crippa, S., Nemir, M., Sarre, A., Johnson, R., Dauvillier, J., Burdet, F., Ibberson, M., Guigo, R., Xenarios, I., Heymans, S., & Pedrazzini, T. (2015). Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs. European Heart Journal. https://doi.org/10.1093/eurheartj/ehu180

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.