Current concepts in the epigenetic regulation of cardiac fibrosis

•Cardiac fibrosis is a major contributor to morbidity and mortality for a growing number of individuals worldwide.•Subcellular and transcriptomal processes have been implicated in the pathogenesis of cardiac fibrosis.•Recent work has revealed that exosomes and epigenetic modifications may have a cri...

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Bibliographic Details
Published in:Cardiovascular pathology 2024-11, Vol.73, p.107673, Article 107673
Main Authors: Fatehi Hassanabad, Ali, Zarzycki, Anna N., Patel, Vaibhav B., Fedak, Paul W. M.
Format: Article
Language:English
Subjects:
cardiac fibrosis
epigenetic modulation
exosomes
heart failure
microRNA
therapeutics
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Summary:•Cardiac fibrosis is a major contributor to morbidity and mortality for a growing number of individuals worldwide.•Subcellular and transcriptomal processes have been implicated in the pathogenesis of cardiac fibrosis.•Recent work has revealed that exosomes and epigenetic modifications may have a critical role in modulating cardiac fibrosis.•While at the early stages of study, precisely targeting epigenetic regulators that have been implicated in pro-fibrotic processes may confer benefits in attenuating cardiac fibrosis. Cardiac fibrosis is a significant driver of congestive heart failure, a syndrome that continues to affect a growing patient population globally. Cardiac fibrosis results from a constellation of complex processes at the transcription, receptor, and signaling axes levels. Various mediators and signaling cascades, such as the transformation growth factor-beta pathway, have been implicated in the pathophysiology of cardiac tissue fibrosis. Our understanding of these markers and pathways has improved in recent years as more advanced technologies and assays have been developed, allowing for better delineation of the crosstalk between specific factors. There is mounting evidence suggesting that epigenetic modulation plays a pivotal role in the progression of cardiac fibrosis. Transcriptional regulation of key pro- and antifibrotic pathways can accentuate or blunt the rate and extent of fibrosis at the tissue level. Exosomes, micro-RNAs, and long noncoding RNAs all belong to factors that can impact the epigenetic signature in cardiac fibrosis. Herein, we comprehensively review the latest literature about exosomes, their contents, and cardiac fibrosis. In doing so, we highlight the specific transcriptional factors with pro- or antifibrotic properties. We also assimilate the data supporting these mediators' potential utility as diagnostic or prognostic biomarkers. Finally, we offer insight into where further work can be done to fill existing gaps to translate preclinical findings better and improve clinical outcomes.
ISSN:1054-8807
1879-1336
1879-1336
DOI:10.1016/j.carpath.2024.107673