Journal
ATHEROSCLEROSIS
Volume 281, Issue -, Pages 150-158Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2018.09.029
Keywords
Epigenetics; Cardiometabolism; Inflammation; Obesity; Type 2 diabetes
Funding
- Sheikh Khalifa's Foundation Assistant Professorship at the Faculty of Medicine, University of Zurich
- Zurich Heart House
- Swiss Heart Foundation
- Swiss Life Foundation
- Kurt und Senta-Hermann Stiftung
- Schweizerische Diabetes-Stiftung
- Holcim Foundation
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Albeit a consistent body of evidence supports the notion that genes influence cardiometabolic features and outcomes, the non-genetic regulation of this process is gaining increasing attention. Plastic chemical changes of DNA/histone complexes - known as epigenetic changes - critically determine gene activity by rapidly modifying chromatin accessibility to transcription factors. In this review, we describe the emerging role of chromatin modifications as fine tuners of gene transcription in adipogenesis, insulin resistance, macrophage polarization, immuno-metabolism, endothelial dysfunction and metabolic cardiomyopathy. Epigenetic processing participates in the dynamic interplay among different organs in the cardiometabolic patient. DNA methylation and post-translational histone modifications in both visceral and subcutaneous adipose tissue enable the transcription of genes implicated in lipo-and adipogenesis, inflammation and insulin resistance. Along the same line, complex networks of chromatin modifying enzymes are responsible for impaired nitric oxide bioavailability and defective insulin signalling in the vasculature, thus leading to reduced capillary recruitment and insulin delivery in the liver, skeletal muscle and adipose tissue. Furthermore, changes in methylation status of IL-4, IFN gamma and Forkhead box P3 (Foxp3) gene loci are crucial for the polarization of immune cells, thus leading to adipose tissue inflammation and atherosclerosis. Cell-specific epigenetic information could advance our understanding of cardiometabolic processes, thus leading to individualized risk assessment and personalized therapeutic approaches in patients with cardiometabolic disturbances. The development of new chromatin modifying drugs indicates that targeting epigenetic changes is a promising approach to reduce the burden of cardiovascular disease in this setting.
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