Non-coding RNAs as therapeutic targets and biomarkers in ischaemic heart disease

The adult heart is a complex, multicellular organ that is subjected to a series of regulatory stimuli and circuits and has poor reparative potential. Despite progress in our understanding of disease mechanisms and in the quality of health care, ischaemic heart disease remains the leading cause of death globally, owing to adverse cardiac remodelling, leading to ischaemic cardiomyopathy and heart failure. Therapeutic targets are urgently required for the protection and repair of the ischaemic heart. Moreover, personalized clinical biomarkers are necessary for clinical diagnosis, medical management and to inform the individual response to treatment. Non-coding RNAs (ncRNAs) deeply influence cardiovascular functions and contribute to communication between cells in the cardiac microenvironment and between the heart and other organs. As such, ncRNAs are candidates for translation into clinical practice. However, ncRNA biology has not yet been completely deciphered, given that classes and modes of action have emerged only in the past 5 years. In this Review, we discuss the latest discoveries from basic research on ncRNAs and highlight both the clinical value and the challenges underscoring the translation of these molecules as biomarkers and therapeutic regulators of the processes contributing to the initiation, progression and potentially the prevention or resolution of ischaemic heart disease and heart failure. Non-coding RNAs are implicated in the pathophysiology of ischaemic heart disease and heart failure. In this Review, Caporali and colleagues examine the biology of these molecules and discuss the potential of non-coding RNAs for translation to the clinic as biomarkers and therapeutics in adverse cardiac remodelling leading to ischaemic heart failure. Ischaemic heart disease causes adverse cardiac remodelling, leading to ischaemic cardiomyopathy and heart failure, and is the leading cause of death globally.Non-coding RNAs (ncRNAs) are functional RNA molecules that are not translated into proteins; these molecules are involved in cardiovascular homeostasis and the regulation of mechanisms that lead to ischaemic heart disease.ncRNAs are being investigated for their capacity to combat ischaemic cardiac remodelling, promote therapeutic angiogenesis and replace cardiomyocyte loss, and as biomarkers of cardiac injury and remodelling.The various classes of ncRNA interact among themselves and with mRNAs and RNA-binding proteins, establishing complex regulatory networks; post-transcriptional modifications expand the therapeutic target repertoire of ncRNAs.ncRNAs are released extracellularly and circulate in biological fluids in protected forms; as such, they have potential as actionable biomarkers, supporting a theranostic approach to personalized medicine.Improved techniques for nucleic acid detection promise the discovery of new ncRNA species, while developments in drug formulation and delivery support the translation of ncRNA therapeutics to clinical trials.