Long noncoding RNA dysregulation in ischemic heart failure

Research output: Contribution to journalArticle

Abstract

Background: Long noncoding RNAs (lncRNAs) are non-protein coding transcripts regulating a variety of physiological and pathological functions. However, their implication in heart failure is still largely unknown. The aim of this study is to identify and characterize lncRNAs deregulated in patients affected by ischemic heart failure. Methods: LncRNAs were profiled and validated in left ventricle biopsies of 18 patients affected by non end-stage dilated ischemic cardiomyopathy and 17 matched controls. Further validations were performed in left ventricle samples derived from explanted hearts of end-stage heart failure patients and in a mouse model of cardiac hypertrophy, obtained by transverse aortic constriction. Peripheral blood mononuclear cells of heart failure patients were also analyzed. LncRNA distribution in the heart was assessed by in situ hybridization. Function of the deregulated lncRNA was explored analyzing the expression of the neighbor mRNAs and by gene ontology analysis of the correlating coding transcripts. Results: Fourteen lncRNAs were significantly modulated in non end-stage heart failure patients, identifying a heart failure lncRNA signature. Nine of these lncRNAs (CDKN2B-AS1/ANRIL, EGOT, H19, HOTAIR, LOC285194/TUSC7, RMRP, RNY5, SOX2-OT and SRA1) were also confirmed in end-stage failing hearts. Intriguingly, among the conserved lncRNAs, h19, rmrp and hotair were also induced in a mouse model of heart hypertrophy. CDKN2B-AS1/ANRIL, HOTAIR and LOC285194/TUSC7 showed similar modulation in peripheral blood mononuclear cells and heart tissue, suggesting a potential role as disease biomarkers. Interestingly, RMRP displayed a ubiquitous nuclear distribution, while H19 RNA was more abundant in blood vessels and was both cytoplasmic and nuclear. Gene ontology analysis of the mRNAs displaying a significant correlation in expression with heart failure lncRNAs identified numerous pathways and functions involved in heart failure progression. Conclusions: These data strongly suggest lncRNA implication in the molecular mechanisms underpinning HF.

Original languageEnglish
Article number183
JournalJournal of Translational Medicine
Volume14
Issue number1
DOIs
Publication statusPublished - Jun 18 2016

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Long Noncoding RNA
Heart Failure
Gene Ontology
Cardiomegaly
Heart Ventricles
Blood Cells
Messenger RNA
Ontology
Blood
Dilated Cardiomyopathy
Genes
Constriction
In Situ Hybridization
Blood Vessels
Biopsy
Biomarkers
Blood vessels

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Long noncoding RNA dysregulation in ischemic heart failure. / Greco, Simona; Zaccagnini, Germana; Perfetti, Alessandra; Fuschi, Paola; Valaperta, Rea; Voellenkle, Christine; Castelvecchio, Serenella; Gaetano, Carlo; Finato, Nicoletta; Beltrami, Antonio Paolo; Menicanti, Lorenzo; Martelli, Fabio.

In: Journal of Translational Medicine, Vol. 14, No. 1, 183, 18.06.2016.

Research output: Contribution to journalArticle

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author = "Simona Greco and Germana Zaccagnini and Alessandra Perfetti and Paola Fuschi and Rea Valaperta and Christine Voellenkle and Serenella Castelvecchio and Carlo Gaetano and Nicoletta Finato and Beltrami, {Antonio Paolo} and Lorenzo Menicanti and Fabio Martelli",
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AU - Greco, Simona

AU - Zaccagnini, Germana

AU - Perfetti, Alessandra

AU - Fuschi, Paola

AU - Valaperta, Rea

AU - Voellenkle, Christine

AU - Castelvecchio, Serenella

AU - Gaetano, Carlo

AU - Finato, Nicoletta

AU - Beltrami, Antonio Paolo

AU - Menicanti, Lorenzo

AU - Martelli, Fabio

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