Epigenetics is involved in the pleiotropic effects of statins

Author(s)

Kayzuka, Cezar ; Rondon-Pereira, Vitoria Carolina ; Tavares, Cecilia Nogueira ; Pachado, Mayra Pacheco ; Monica, Fabiola Zakia ; Tanus-Santos, Jose Eduardo ; Lacchini, Riccardo

• Document type: Journal article
• Source: EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY; v. N/A, p. 13-pg., 2025-04-19.

Abstract

IntroductionStatins have significantly reduced mortality from cardiovascular diseases by lowering serum cholesterol levels. Beyond their lipid-lowering effects, statins improve vascular function, reduce inflammation, decrease reactive oxygen species (ROS) formation, and stabilize atherosclerotic plaques. However, the mechanisms underlying these pleiotropic effects remain unclear. Area coveredThis narrative review summarizes and discusses epigenetic mechanisms that may explain part of the pleiotropic effects of statins. This approach allows for a reevaluation of statin use beyond its cholesterol-lowering benefits. A structured search was conducted in the PubMed and Scopus databases using specific search terms, including articles published up to August 2024.Expert opinionThe pleiotropic effects of statins, including those mediated by the isoprenoid pathway, partially explain their clinical benefits. By inhibiting histone deacetylases (HDACs, the 'erasers') and DNA methyltransferases (DNMTs, the 'writers'), statins promote increased histone acetylation and reduced DNA methylation at gene promoter regions. These epigenetic modifications enhance chromatin accessibility, facilitating gene transcription and protecting the cardiovascular system. Further investigation into these epigenetic mechanisms could support the repositioning of statins for broader therapeutic applications. Statins may have benefits extending beyond their role in managing hypercholesterolemia, as their pleiotropic effects contribute to the prevention of cardiovascular disease-related mortality through mechanisms independent of LDL cholesterol reduction. (AU)

• FAPESP's process: 20/11740-9 - Evaluation of epigenetic mechanisms in response to drug treatments in genes related to Hypertension in an experimental animal model
• Grantee: Cezar Kayzuka Cotta Filho
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/18312-2 - EVALUATION OF THE EPIGENETIC EFFECTS OF ATORVASTATIN ON THE REGULATION OF EXPRESSION OF GENES RELATED TO NITRIC OXIDE IN EXPERIMENTAL HYPERTENSION MODEL
• Grantee: Riccardo Lacchini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/12072-5 - Influence of the extracellular matrix metalloproteinases on Depressive Disorder: study of biochemical and genetic biomarkers
• Grantee: Riccardo Lacchini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/07921-3 - Aging-associated Pulmonary Vascular Injury via NOS1/3-mediated oxidative stress
• Grantee: Cezar Kayzuka Cotta Filho
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 19/10748-9 - Evaluation of atorvastatin pleiotropic effects on the regulation of epigenetics mechanisms over specific gens linked to nitric oxide on a hypertension experimental model
• Grantee: Cezar Kayzuka Cotta Filho
• Support Opportunities: Scholarships in Brazil - Master