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Rewriting Heart Health: Epigenetic Drugs in Cardiovascular Medicine
Natalia Atzemian1,2, Ludovica Di Venanzio1,2, Shafeeq Ahmed Mohammed1,2
1Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.
Abstract:
Cardiovascular disease reflects not only genetic predisposition and haemodynamic stress but also reversible alterations in chromatin organisation and transcriptional programming, a layer of regulation that is, in principle, amenable to pharmacological intervention. Purpose-built epigenetic drugs, DNA methyltransferase inhibitors, histone deacetylase inhibitors, histone acetyltransferase inhibitors, bromodomain and extraterminal domain inhibitors, enhancer of zeste homolog 2 inhibitors, and RNA-based therapeutics, target this machinery directly. In parallel, established cardiovascular therapies, including statins, renin-angiotensin-aldosterone system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, antithrombotic agents, sodium-glucose cotransporter-2 inhibitors, and incretin-based therapies, appear to modulate the epigenome as an underappreciated component of their action, a concept termed "pharmaco-epigenetics". This review appraises both axes side by side, with explicit attention to clinical maturity, including the level of evidence, human validation, development stage, and the interpretation of hypothesis-generating findings. Key translational barriers, cardiac-targeted delivery, biomarkers of target engagement, and interindividual epigenetic variability, are outlined alongside priorities for future trial design.
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