Epigenetic therapies in heart failure

Abstract

Heart failure (HF) is a dominant cause of morbidity and mortality in the developed world, with available pharmacotherapies limited by high rates of residual mortality and a failure to directly target the changes in cell state that drive adverse cardiac remodeling. Pathologic cardiac remodeling is driven by stress-activated cardiac signaling cascades that converge on defined components of the chromatin regulatory apparatus in the nucleus, triggering broad shifts in transcription and cell state. Thus, studies focusing on how cytosolic signaling pathways couple to the nuclear gene control machinery has been an area of therapeutic interest in HF. In this review, we discuss current concepts pertaining to the role of chromatin regulators in HF pathogenesis, with a focus on specific proteins and RNA-containing macromolecular complexes that have shown promise as druggable targets in the experimental setting.

A novel chemical-combination screen in zebrafish identifies epigenetic small molecule candidates for the treatment of Duchenne muscular dystrophy

“…While some epigenetic small molecules have off-target or solubility issues, there is potential for optimizing dosing or using these chemicals as lead compounds for further analyses [81,83]. In addition, there are growing numbers of examples showing that epigenetic small molecules synergize with each other or with other compounds to target different diseases, including cancer and heart disease [59,[81][82][83][84][85]. In our work here, we show an example of a combination of two epigenetic small molecules that are beneficial for dmd mutant zebrafish.…”

Targeting AMP-Activated Protein Kinase in Aging-Related Cardiovascular Diseases

“…Heart failure is the final stage in the development of heart disease and a dominant cause of morbidity and mortality in the developed world [78]. It commonly affects older population and with the extension of life expectancy and the improvement of medical and health conditions, the number of patients with heart failure is expected to increase [79].…”

A novel drug-combination screen in zebrafish identifies epigenetic small molecule candidates for Duchenne muscular dystrophy

“…While some epigenetic drugs have off-target or solubility issues, there is potential for optimizing dosing or using these drugs as lead compounds for further analyses (Abdelfatah et al, 2016; Bai et al, 2019). In addition, there are growing numbers of examples showing that epigenetic small molecules synergize with each other or with other drugs to target different diseases, including cancer and heart disease (Abdelfatah et al, 2016; Ahuja et al, 2016; Alexanian et al, 2019; Bai et al, 2019; Huber et al, 2011; Mazur et al, 2015). In our work here, we show an example of a combination of two epigenetic drugs that are beneficial for dmd zebrafish.…”