Fluid-based assays and precision medicine of cardiovascular diseases: the ‘hope’ for Pandora’s box?

Abstract

Progresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field.

Epigenetic-sensitive liquid biomarkers and personalised therapy in advanced heart failure: a focus on cell-free DNA and microRNAs

“…Moreover, EMB still plays a role in this field but certainly has a relevant role in post-transplant monitoring. 11 DCM is regarded not as a single disease entity, but rather as heterogeneous phenotype with a final common response of the myocardium to a number of genetic and environmentally acquired insults. Common therapies and devices, such as β-blockers, renin-angiotensin-aldosterone inhibitors and cardiac resynchronisation therapy (CRT), can induce 'LV reverse remodelling', characterised by a decrease in LV volume and improved systolic function in patients with DCM.…”

“…5 7 The major epigenetic mechanisms are DNA methylation, histone and non-histone modifications, and non-codingRNA molecules, mainly microRNA (miRNAs) which control gene expression without altering DNA sequence in several cardiovascular diseases. [8][9][10][11][12][13] Remarkably, advanced next-generation sequencing (NGS) platforms emphasised the putative useful role of liquid-based assays for detecting cell-free DNA (cfDNA) and miRNAs to improve precision medicine of HF. 11 14 15 We briefly summarise genetic determinants involved in DCM diagnosis and progression of HF (figure 1).…”

Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review

“…Network medicine relies on potent bioinformatic tools analyzing multilayered disease phenotypes within the framework of molecular interaction (interactome), thus surpassing the current reductionist approach [6][7][8]82]. e main goal is to discover novel molecular alterations able to alter the interactome flow and define the causative relationship between candidate genes and diseases [6][7][8]82]. Remarkably, network medicine might redefine complex diseases by focusing on their underlying pathobiological molecules, leading to a new classification system in relation to the current reductionist approach.…”

“…In contrast to genetic mutations, epimutations show a reversible nature. Small molecules, named epi-drugs, including the DNA methyltransferase inhibitors (DNMTi) and histone deacethyltransferase (HDAC) inhibitors, as HDACi, or activators, as HDACa, can revert aberrant epigenetic changes, thus suggesting the possible development of useful innovative drugs able to prevent or revert molecular defects underlying human diseases [5][6][7]. Improvements in nextgeneration sequencing (NGS) tools and bioinformatic algorithm development are providing the opportunity to trace subjects in a multilayered network by using "omics" data, in order to further dissect genome-environment interactions [8].…”

Early targeted DNA methylation profiling of CD04+/CD08+ T cells reveals pathogenic mechanisms in different stages of impaired glucose homeostasis Cardiovascular Diabetology

“…Since DNA methylation at regulatory regions is highly correlated with cell-specific patterns of repressive chromatin marks (7), we chose the reduced representation bisulfite sequencing (RRBS) platform which provides an enrichment of both promoters and CpG islands (32). Thus, the identification of novel early and non-invasive molecular biomarkers by using liquid-based assays [33] could help physicians to select high risk hyperglycemic patients, allowing a selective phenotyping of the prediabetic patient and help to stratify the risk of developing CHD and vascular complications.…”