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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. [ABSTRACT FROM AUTHOR]

Significance: microRNA-210 (miR-210) is the master hypoxia-inducible miRNA (hypoxamiR) since it has been found to be significantly upregulated under hypoxia in a wide range of cell types. Recent advances: Gene ontology analysis of its targets indicates that miR-210 modulates several aspects of cellular response to hypoxia. Due to its high pleiotropy, miR-210 not only plays a protective role by fine-tuning mitochondrial metabolism and inhibiting red-ox imbalance and apoptosis, but it can also promote cell proliferation, differentiation, and migration, substantially contributing to angiogenesis. Critical issues: As most miRNAs, modulating different gene pathways, also miR-210 can potentially lead to different and even opposite effects, depending on the physio-pathological contexts in which it acts. Future direction: The use of miRNAs as therapeutics is a fast growing field. This review aimed at highlighting the role of miR-210 in angiogenesis in the context of ischemic cardiovascular diseases and diabetes in order to clarify the molecular mechanisms underpinning miR-210 action. Particular attention will be dedicated to experimentally validated miR-210 direct targets involved in cellular processes related to angiogenesis and diabetes mellitus, such as mitochondrial metabolism, redox balance, apoptosis, migration, and adhesion. Antioxid. Redox Signal. 36, 685–706. [ABSTRACT FROM AUTHOR]