Circulating non-coding RNAs in biomarker-guided cardiovascular therapy: a novel tool for personalized medicine?

Abstract

Current clinical guidelines emphasize the unmet need for technological innovations to guide physician decision-making and to transit from conventional care to personalized cardiovascular medicine. Biomarker-guided cardiovascular therapy represents an interesting approach to inform tailored treatment selection and monitor ongoing efficacy. However, results from previous publications cast some doubts about the clinical applicability of biomarkers to direct individualized treatment. In recent years, the non-coding human transcriptome has emerged as a new opportunity for the development of novel therapeutic strategies and biomarker discovery. Non-coding RNA (ncRNA) signatures may provide an accurate molecular fingerprint of patient phenotypes and capture levels of information that could complement traditional markers and established clinical variables. Importantly, ncRNAs have been identified in body fluids and their concentrations change with physiology and pathology, thus representing promising non-invasive biomarkers. Previous publications highlight the translational applicability of circulating ncRNAs for diagnosis and prognostic stratification within cardiology. Numerous independent studies have also evaluated the potential of the circulating non-coding transcriptome to predict and monitor response to cardiovascular treatment. However, this field has not been reviewed in detail. Here, we discuss the state-of-the-art research into circulating ncRNAs, specifically microRNAs and long non-coding RNAs, to support clinical decision-making in cardiovascular therapy. Furthermore, we summarize current methodological and conceptual limitations and propose future steps for their incorporation into personalized cardiology. Despite the lack of robust population-based studies and technical barriers, circulating ncRNAs emerge as a promising tool for biomarker-guided therapy.

Significance of non-coding circular RNAs and micro RNAs in the pathogenesis of cardiovascular diseases

“…Apart from their use as disease biomarkers, miRNAs have also proven to be useful in evaluating patient response to the available therapies during the course of treatments and also to understand whether a patient will be responsive to a given treatment. 116 117 Also, miRNAs are being tested as drugs for cardiovascular diseases in multiple preclinical studies and have proven to be efficacious. However, considering that miRNAs and circRNAs have multiple cellular targets and may show their effects in organs not directly involved in the disease pathogenesis, attempts are being made to improve the in vivo specificity of miRNA mimics.…”

Plasma circular RNA hsa_circ_0001445 and coronary artery disease: Performance as a biomarker

“…6 In this context, the noncoding transcriptome represents a novel and poorly explored source of diagnostic and prognostic tools for the management of cardiovascular disease (CVD). 7 In particular, circular RNAs (circRNAs), a subclass of the noncoding RNA (ncRNA) superfamily, have recently gained great interest in biomarker development. 8,9 Due to their covalently closed loop structure, circRNAs are protected from exonuclease-mediated degradation and have a longer half-life than linear RNAs.…”

Circulating miRNAs as Diagnostic Biomarkers for Parkinson’s Disease

“…However, several studies showed that α-synuclein levels in blood or CSF lack discrimination power and specificity ( Malek et al, 2014 ; Goldman et al, 2018 ). Next to proteins and metabolites, circulating microRNAs (miRNAs) were previously shown to be useful biomarkers in other pathologies, e.g., cancer ( Jamali et al, 2018 ) or cardiovascular disease ( de Gonzalo-Calvo et al, 2018 ). miRNAs are small non-coding RNAs involved in the regulation of gene expression.…”