Abstract
Heart disease represents one of the main challenges in modern medicine with insufficient treatment options. Whole genome sequencing allowed for the discovery of several classes of non-coding RNA (ncRNA) and widened our understanding of disease regulatory circuits. The intrinsic ability of long ncRNAs (lncRNAs) and circular RNAs (circRNAs) to regulate gene expression by a plethora of mechanisms make them candidates for conceptually new treatment options. However, important questions remain to be addressed before we can fully exploit the therapeutic potential of these molecules. Increasing our knowledge of their mechanisms of action and refining the approaches for modulating lncRNAs expression are just a few of the challenges we face. The accurate identification of novel lncRNAs is hampered by their relatively poor cross-species sequence conservation and their low and context-dependent expression pattern. Nevertheless, progress has been made in their annotation in recent years, while a few experimental studies have confirmed the value of lncRNAs as new mechanisms in the development of cardiac hypertrophy and other cardiovascular diseases. Here, we explore cardiac lncRNA biology and the evidence that this class of molecules has therapeutic benefit to treat cardiac hypertrophy.
Highlights
Heart failure (HF) is a highly prevalent disease and a leading cause of hospitalization and death that affects 23 million patients worldwide (Ziaeian and Fonarow, 2016)
Cardiac hypertrophy is accompanied by a plethora of biochemical, molecular, metabolic and extracellular changes that provoke a decrease of pump function over time rather than preserving it, resulting in overt heart failure and a propensity for the occurrence of lethal arrhythmias (Dirkx et al, 2013)
A better understanding of the molecular underpinnings of cardiac hypertrophy will help to clarify the maladaptive nature of this disease and may open new therapeutic targets for future treatment of hypertrophic heart diseases to reduce the number of HF patients
Summary
Heart failure (HF) is a highly prevalent disease and a leading cause of hospitalization and death that affects 23 million patients worldwide (Ziaeian and Fonarow, 2016). Van Heesch and colleagues (van Heesch et al, 2019) used ribosome profiling to capture ribosomal footprints on human cardiac transcripts and inferred actively translated sORFs that encode previously unknown microproteins in over 169 lncRNAs and 40 circular RNAs that are expressed in the heart. Cardiac Hypertrophy-Related Factor (CHRF) is upregulated in both hypertrophic mouse hearts and human biopsies of patients with heart failure and functions as a sponge for miR-489, regulating Myeloid differentiation primary response gene 88 (Myd88) as downstream target of miR-489.
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