Emerging epigenetic therapies of cardiac fibrosis and remodeling in heart failure: from basic mechanisms to early clinical development.

Cardiovascular diseases and specifically heart failure (HF) impact global health and impose a significant economic burden on society. Despite current advances in standard of care, the risks for death and readmission of HF patients remain unacceptably high and new therapeutic strategies to limit HF progression are highly sought. In disease settings, persistent mechanical or neurohormonal stress to the myocardium triggers maladaptive cardiac remodeling, which alters cardiac function and structure at both the molecular and cellular level. The progression and magnitude of maladaptive cardiac remodeling ultimately leads to the development of HF. Classical therapies for HF are largely protein-based and mostly are targeted to ameliorate the dysregulation of neuroendocrine pathways and halt averse remodeling. More recently, investigation of novel molecular targets and the application of cellular therapies, epigenetic modifications, and regulatory RNAs has uncovered promising new avenues to address HF. In this review we summarize the current knowledge on novel cellular and epigenetic therapies and focus on two non-coding RNA-based strategies that reached the phase of early clinical development to counteract cardiac remodeling and HF. The current status of the development of translating those novel therapies to clinical practice, limitations and future perspectives are additionally discussed.