Unlocking CRISPR: Epigenetics in Cardiac Hypertrophy

Abstract

Cardiac hypertrophy, characterized by the enlargement of heart muscle cells in response to chronic stressors such as hypertension and genetic mutations, is a significant risk factor for heart failure and sudden cardiac death. While current treatments focus on symptom management, they do not directly address the underlying molecular mechanisms driving pathological heart remodeling. This paper explores the potential of epigenetic regulation and CRISPR-based technologies as targeted, reversible therapies for cardiac hypertrophy. Epigenetic modifications—including DNA methylation, histone modifications, and non-coding RNA activity—play a central role in modulating gene expression associated with cardiac growth and remodeling. Dysregulation of these processes can silence protective genes or activate pro-hypertrophic pathways, contributing to disease progression.

Recent advances in CRISPR/dCas9 systems have enabled precise epigenetic editing without altering the genome. Tools such as dCas9-TET and dCas9-DNMT can add or remove methyl groups at targeted loci to modulate the gene expression involved in cardiac hypertrophy. Similarly, dCas9 fused with histone-modifying enzymes allows for site-specific acetylation or deacetylation of chromatin, offering a reversible method to turn genes on or off. Preclinical studies in mammalian models have demonstrated the therapeutic potential of these systems, showing effective reversal of maladaptive gene expression and normalization of cardiac structure and function. Despite these promising developments, challenges remain regarding off-target effects, delivery efficiency, and the high cost of gene-based therapies.

This review highlights the promise of CRISPR-based epigenetic editing as a transformative therapeutic strategy for cardiac hypertrophy. By providing a non-permanent, programmable approach to rewire gene expression, this technology holds potential not only for improved treatment of hypertrophic cardiomyopathy but also as a blueprint for addressing other complex, multifactorial diseases in a precise and personalized manner.