Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives

Abstract

Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well as in health and cardiovascular disease. About 99% of the human genome do not encode proteins, but are transcriptionally active representing a broad spectrum of non-coding RNAs (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have been identified as critical novel regulators of cardiovascular risk factors and cell functions and are thus important candidates to improve diagnostics and prognosis assessment. Beyond this, ncRNAs are rapidly emgerging as fundamentally novel therapeutics. On a first level, ncRNAs provide novel therapeutic targets some of which are entering assessment in clinical trials. On a second level, new therapeutic tools were developed from endogenous ncRNAs serving as blueprints. Particularly advanced is the development of RNA interference (RNAi) drugs which use recently discovered pathways of endogenous short interfering RNAs and are becoming versatile tools for efficient silencing of protein expression. Pioneering clinical studies include RNAi drugs targeting liver synthesis of PCSK9 resulting in highly significant lowering of LDL cholesterol or targeting liver transthyretin (TTR) synthesis for treatment of cardiac TTR amyloidosis. Further novel drugs mimicking actions of endogenous ncRNAs may arise from exploitation of molecular interactions not accessible to conventional pharmacology. We provide an update on recent developments and perspectives for diagnostic and therapeutic use of ncRNAs in cardiovascular diseases, including atherosclerosis/coronary disease, post-myocardial infarction remodelling, and heart failure.

KCNQ1OT1, HIF1A‐AS2 and APOA1‐AS are promising novel biomarkers for diagnosis of coronary artery disease

“…Furthermore, in the present study, we focused on only a subset of lncRNAs that are relevant to cardiac disease. Thus, our findings do not provide a panorama for a comprehensive understanding of all lncRNAs identified thus far but might have missed many other important lncRNAs (such as the lncRNAs CoroMarker and LncPPARσ) that were not included in the present study for their potential as CAD biomarkers . Nonetheless, the lncRNAs selected for our study are those that have been shown to be able to cause cardiac disorders or are abundantly expressed in heart cells.…”

“…Some factors include the choice of material, sample isolation, detection and processing techniques as well as normalization strategies and the influence of drugs and other, noncardiac disease and phenotypes . Here, we chose PBMC samples and therefore need to consider alterations in lncRNA levels between PBMCs and plasma.…”

The novel regulatory role of lncRNA‐miRNA‐mRNA axis in cardiovascular diseases

“…Unlike lncRNAs, miRNAs are a family of evolutionarily conserved, endogenous, ncRNAs approximately 22 nt in length, that can bind to the 3′‐untranslated region (3′‐UTR) of mRNAs through imperfect complementarity . miRNAs may regulate more than 30% of genes and play a significant role in the regulation of biological activities in cells by inhibiting target mRNA translation or promoting mRNA degradation …”

“…14 miRNAs may regulate more than 30% of genes and play a significant role in the regulation of biological activities in cells by inhibiting target mRNA translation or promoting mRNA degradation. 15,16 It is of note that lncRNA and miRNA can modulate the initiation and progression of CVDs via regulating different molecular mechanisms. For instance, the inhibition of Meg3 suppressed cardiac fibrosis and hypertrophy by decreasing MMP-2 expression.…”

Genetic Dissection of the Impact of miR-33a and miR-33b during the Progression of Atherosclerosis

“…Targeting miRNAs is a promising therapeutic approach, as they are dysregulated during and involved in the development of many different disease states (Barwari et al, 2016; Poller et al, 2017). Recent work has elucidated the role of miRNAs in the development of numerous metabolic conditions including obesity, Type II diabetes and cardiovascular disease, which are responsible for the majority of chronic illnesses and deaths in the United States and other developed countries.…”