Epigenetics is involved in the pleiotropic effects of statins

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY; v. N/A, p. 13-pg., 2025-04-19.

Resumo

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)

• Processo FAPESP: 20/11740-9 - Avaliação dos mecanismos epigenéticos na resposta a tratamentos farmacológicos nos genes relacionados à Hipertensão Arterial em modelo experimental animal
• Beneficiário: Cezar Kayzuka Cotta Filho
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/18312-2 - Avaliação dos efeitos epigenéticos da atorvastatina sobre a regulação da expressão de genes relacionados ao óxido nítrico em modelo experimental de hipertensão
• Beneficiário: Riccardo Lacchini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/12072-5 - Influência de metaloproteinases de matriz extracelular sobre o Transtorno Depressivo: estudo de biomarcadores bioquímicos e genéticos
• Beneficiário: Riccardo Lacchini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/07921-3 - Lesão vascular pulmonar associada ao envelhecimento via estresse oxidativo mediado por NOS1/3
• Beneficiário: Cezar Kayzuka Cotta Filho
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 19/10748-9 - Avaliação do efeito pleiotrópico da atorvastatina na regulação dos mecanismos epigenéticos nos genes específicos relacionados ao óxido nítrico em modelo experimental de hipertensão
• Beneficiário: Cezar Kayzuka Cotta Filho
• Modalidade de apoio: Bolsas no Brasil - Mestrado