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Review
. 2024 Sep 27;30(1):161.
doi: 10.1186/s10020-024-00939-z.

Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies

Giulia Damiano  1 , Raffaella Rinaldi  1 , Angela Raucci  2 , Chiara Molinari  3 , Annalisa Sforza  1 , Sergio Pirola  4 , Francesco Paneni  5   6 , Stefano Genovese  3 , Giulio Pompilio  1   7 , Maria Cristina Vinci  8
Affiliations
Review

Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies

Giulia Damiano et al. Mol Med. .

Abstract

The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabetes and the prevention or for slowing down its complications, aiming to alleviate the personal and social burden of the disease.This review addresses current knowledge of the pathophysiological links between diabetes and cardiovascular complications, focusing on the role of epigenetic modifications, including DNA methylation and histone modifications. In addition, although the treatment of complications of diabetes with "epidrugs" is still far from being a reality and faces several challenges, we present the most promising molecules and approaches in this field.

Keywords: Cardiovascular complications; Diabetes; Epidrugs GLP-1RA; Epigenetics.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Mechanism of function of DNMT3A. (A) DNMT3A recognizes and bind histone H3 when methyl-free and this interaction causes a conformational change that led DNMT3A to an active state. Thus, DNMT3A is ready to catalyse DNA methylation. (B) Schematic representation of repression of transcriptional activity mediated by DNA methylation
Fig. 2
Fig. 2
(A) Representative structure of BET proteins. (B) Functions of BET family member BRD4 in the regulation of promoter. BRD4 binds to acetylated lysine (COCH3) in histones or transcription factors (TF) via its BD1 and BD2 domains. The binding of acetylated histones by BRD4, at transcription start sites (TSS), mediates transcriptional co-activation and elongation via RNA polymerase II (RNA pol II) and Mediator (Med) and positive transcription elongation factor B (P-TEFb) signaling complexes
Fig. 3
Fig. 3
(A) Epigenetic-mediated upregulation of the adaptor protein p66shc. (B) Set7-mediated regulation of RELA gene transcription
Fig. 4
Fig. 4
Representative mechanism of action of the BET inhibitor apabetalone
See this image and copyright information in PMC

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