Epigenetic modifications and emerging therapeutic targets in cardiovascular aging and diseases

The intricate mechanisms contributing to the onset and progression of cardiovascular diseases remain incompletely understood. However, epigenetics, which regulates gene expression without altering the DNA sequence, is increasingly providing valuable insights into these mechanisms and their heritable effects.

This review focuses on the role of epigenetic regulation in cardiovascular aging and disease, highlighting key epigenetic enzymes that serve as “writers” and “erasers” of epigenetic modifications. These include DNA methyltransferases (DNMTs), histone acetyltransferases (HATs), and histone deacetylases (HDACs). Additionally, we discuss the “readers” of these modifications, such as 5-methylcytosine binding domain proteins, and the “erasers,” including ten-eleven translocation (TET) proteins, which play crucial roles in modulating the epigenetic landscape.

Emerging research has also identified the significance of RNA methylation, particularly N6-methyladenosine (m6A), in cardiovascular pathogenesis. Given its influence on RNA stability, splicing, and translation, m6A methylation represents a promising area for further exploration in cardiovascular disease research.

We also summarize potential therapeutic targets within the epigenetic framework, focusing on key enzymes and their inhibitors. Notably, DNMT inhibitors such as 5-azacytidine and decitabine, as well as HDAC inhibitors like belinostat and givinostat, have already been approved by the FDA for treating malignancies. These drugs may hold promise for repurposing in the treatment of cardiovascular diseases.

Furthermore, we explore novel histone modifications and their associated enzymes, which are emerging as potential therapeutic targets. By integrating findings from recent studies involving patients with cardiovascular aging and disease, this review aims to provide a comprehensive and updated perspective on advancements in epigenetic modification within the field of cardiovascular research. GNE-781