Epi-Drugs in Heart Failure

Abstract

Unveiling the secrets of genome’s flexibility does not only foster new research in the field, but also gives rise to the exploration and development of novel epigenetic-based therapies as an approach to alleviate disease phenotypes. A better understanding of chromatin biology (DNA/histone complexes) and non-coding RNAs (ncRNAs) has enabled the development of epigenetic drugs able to modulate transcriptional programs implicated in cardiovascular diseases. This particularly applies to heart failure, where epigenetic networks have shown to underpin several pathological features, such as left ventricular hypertrophy, fibrosis, cardiomyocyte apoptosis and microvascular dysfunction. Targeting epigenetic signals might represent a promising approach, especially in patients with heart failure with preserved ejection fraction (HFpEF), where prognosis remains poor and breakthrough therapies have yet to be approved. In this setting, epigenetics can be employed for the development of customized therapeutic approaches thus paving the way for personalized medicine. Even though the beneficial effects of epi-drugs are gaining attention, the number of epigenetic compounds used in the clinical practice remains low suggesting that more selective epi-drugs are needed. From DNA-methylation changes to non-coding RNAs, we can establish brand-new regulations for drug targets with the aim of restoring healthy epigenomes and transcriptional programs in the failing heart. In the present review, we bring the timeline of epi-drug discovery and development, thus highlighting the emerging role of epigenetic therapies in heart failure.

Bibliometric and visual analysis of RAN methylation in cardiovascular disease

“…NO availability and mitochondrial respiratory chain protein expression were affected to treat obesity and age-related early microvascular endothelial dysfunction ( 50 ). The team also reviewed drugs with known epigenetic effects and potential use in HF ( 51 ), including resveratrol ( 52 ), curcumin ( 53 ), and danshen ( 54 ).…”

“…Third, Sarah Costantino suggested that studying cell-specific epigenetic information and developing chromatin modification drugs could provide a personalized risk assessment and treatment for patients with cardiometabolic disorders ( 51 ). The team examined the effects of hypoxia and hypertrophy stimulation on cardiomyocyte function and methylation levels and found that both resulted in epigenetic-driven upregulation of tenascin C and subsequent damage to cardiomyocyte energy metabolism, revealing the role of RNA methylation in the pathogenesis of CVD ( 59 ).…”

AQP5-1364A/C Polymorphism Affects AQP5 Promoter Methylation

“…Regarding the clinical application of our findings, we can only speculate. As the A-allele is associated with decreased promoter methylation, increased AQP5 expression [ 10 ] and worse outcome in sepsis, the treatment with epigenetic drugs could maybe provide benefit [ 32 ]. Here, a targeted methylation of A-allele carriers might be beneficial in sepsis treatment.…”

Molecular perspectives in hypertrophic heart disease: An epigenetic approach from chromatin modification

“…Frontiers in Cell and Developmental Biology frontiersin.org modulation of genes such as MMP2 (matrix metalloprotease-2) and TGFβ receptor III (Gorica et al, 2022). Micro RNAs are very suitable as markers or therapy for some neoplastic diseases.…”

“…miRNA-133 and miRNA-131 correlate to cardiac hypertrophy ( Statello et al, 2021 ). miRNA-21 plays a role in HF because of the modulation of genes such as MMP2 (matrix metalloprotease-2) and TGFβ receptor III ( Gorica et al, 2022 ). Micro RNAs are very suitable as markers or therapy for some neoplastic diseases.…”