New Mechanisms of Vascular Dysfunction in Cardiometabolic Patients: Focus on Epigenetics
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REVIEW ARTICLE
New Mechanisms of Vascular Dysfunction in Cardiometabolic Patients: Focus on Epigenetics Samuele Ambrosini1 · Shafeeq A. Mohammed1 · Thomas F. Lüscher1,2 · Sarah Costantino1 · Francesco Paneni1,3,4 Received: 23 June 2020 / Accepted: 21 July 2020 © Italian Society of Hypertension 2020
Abstract Epigenetic processing takes centre stage in cardiometabolic diseases (obesity, metabolic syndrome, type 2 diabetes, hypertension), where it participates in adiposity, inflammation, endothelial dysfunction, vascular insulin resistance and atherosclerosis. Epigenetic modifications, defined as heritable changes in gene expression that do not entail mutation in the DNA sequence, are mainly induced by environmental stimuli (stress, pollution, cigarette smoking) and are gaining considerable interest due to their causal role in cardiovascular disease, and their amenability to pharmacological intervention. Importantly, epigenetic modifications acquired during life can be transmitted to the offspring and exert their biological effects across multiple generations. Indeed, such transgenerational transmission of epigenetic signals may contribute to anticipating cardiovascular and metabolic disease phenotypes already in children and young adults. A deeper understanding of environmental factors and their effects on the epigenetic machinery and transcriptional programs is warranted to develop effective mechanism-based therapeutic strategies. The clinical application of epigenetic drugs—also known as “epi-drugs”—is currently exploding in the field of cardiovascular disease. The present review describes the main epigenetic networks underlying cardiometabolic alterations and sheds light on specific points of intervention for pharmacological reprogramming in this setting. Keywords Epigenetics · Metabolic syndrome · Cardiovascular disease · Endothelial dysfunction
1 The Growing Burden of Cardiometabolic Disturbances Prevalence of obesity is dramatically increasing worldwide and associates with cardiometabolic disorders, morbidity and increased mortality rates [1]. Alarmingly, this phenomenon does not only affect adults but also children. Since 1980 prevalence of obesity has almost doubled and, according to the latest estimate of the Global Burden of Disease study, over 600 million adults and 100 million children are currently obese, and these numbers are projected to steadily * Francesco Paneni [email protected] 1
Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, 8952 Schlieren, Switzerland
2
Cardiology, Royal Brompton and Harefield Hospital Trust and Imperial College London, London SW3 6NP, UK
3
University Heart Center, Cardiology, University Hospital Zurich, Zurich, Switzerland
4
Department of Research and Education, University Hospital Zurich, Zurich, Switzerland
increase in the decades to come [2]. The consensus for the diagnosis of metabolic syndrome (MetS), approved by the American Heart Association and the International Diabetes Federation, is the concomitant presence of at le
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