Epigenetics of Early Cardiometabolic Disease: Mechanisms and Precision Medicine

Baccarelli, Andrea A.; Ordovas, José M.

doi:10.1161/circresaha.123.322135

Cited by 12 publications

(6 citation statements)

References 124 publications

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“…These changes in epigenetic marks have been found in a variety of tissues, including sperm, which may indicate possible transgenerational effects [ 54 ]. In humans, several epidemiological studies were able to correlate exposure to chemicals and changes in epigenetic markers, which may support current efforts towards precision prevention [ 55 , 56 ]. Most of the studies considered these epigenetic changes as possible markers of toxicity, in particular long-term toxicity [ 54 ].…”

Section: Long-term Adaptation and Epigeneticsmentioning

confidence: 99%

Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways

Tomkiewicz,

Coumoul,

Nioche

et al. 2024

Phil. Trans. R. Soc. B

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Organisms adapt to their environment through different pathways. In vertebrates, xenobiotics are detected, metabolized and eliminated through the inducible xenobiotic-metabolizing pathways (XMP) which can also generate reactive toxic intermediates. In this review, we will discuss the impacts of the chemical exposome complexity on the balance between detoxication and side effects. There is a large discrepancy between the limited number of proteins involved in these pathways (few dozens) and the diversity and complexity of the chemical exposome (tens of thousands of chemicals). Several XMP proteins have a low specificity which allows them to bind and/or metabolize a large number of chemicals. This leads to undesired consequences, such as cross-inhibition, inefficient metabolism, release of toxic intermediates, etc. Furthermore, several XMP proteins have endogenous functions that may be disrupted upon exposure to exogenous chemicals. The gut microbiome produces a very large number of metabolites that enter the body and are part of the chemical exposome. It can metabolize xenobiotics and either eliminate them or lead to toxic derivatives. The complex interactions between chemicals of different origins will be illustrated by the diverse roles of the aryl hydrocarbon receptor which binds and transduces the signals of a large number of xenobiotics, microbiome metabolites, dietary chemicals and endogenous compounds. This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.

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Section: Long-term Adaptation and Epigeneticsmentioning

confidence: 99%

Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways

Tomkiewicz,

Coumoul,

Nioche

et al. 2024

Phil. Trans. R. Soc. B

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“…Epigenetic changes, resulting from interconnections among genetic, environmental, social, and lifestyle factors, may help to elucidate the biological basis for heterogeneous manifestations of CKM syndrome. 51 A better understanding is also needed regarding multiple MetS subtypes (eg, insulin resistance dominant, lipid dominant, vascular dominant) and the variability in the end organ-related manifestations of CKM syndrome.…”

Section: Understanding the Heterogeneity Within Ckm Syndromementioning

confidence: 99%

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association

Ndumele,

Neeland,

Tuttle

et al. 2023

Circulation

131

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A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

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“…This program promoted the rapid dissemination of precision medicine worldwide. 2 Moreover, the availability of high-throughput gene sequencing technology, 3 as well as the importance of proteomics, metabolomics, transcriptomics, and epigenetics spurred interest in thoroughly understanding human disease, 4 – 8 eventually accelerating the development of precision medicine. Precision medicine has been defined in a variety of ways depending on the perspective of researchers.…”

Section: Introductionmentioning

confidence: 99%

New clinical trial design in precision medicine: discovery, development and direction

Duan,

Qin,

Jiao

et al. 2024

Sig Transduct Target Ther

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In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to the underestimation of the significant heterogeneity across participants in traditional “one-size-fits-all” trials, patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket, umbrella, and platform trial designs under the master protocol framework. In recent years, the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities. Despite the rapid increase in the number of basket, umbrella, and platform trials, the current clinical and research understanding of these new trial designs, as compared with traditional trial designs, remains limited. The majority of the research focuses on methodologies, and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs. Therefore, we provide this comprehensive review of the discovery and development of basket, umbrella, and platform trials and their underlying logic from the perspective of precision medicine. Meanwhile, we discuss future directions on the potential development of these new clinical design in view of the “Precision Pro”, “Dynamic Precision”, and “Intelligent Precision”. This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic, which be essential to accelerate the progression of precision medicine.

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Epigenetics of Early Cardiometabolic Disease: Mechanisms and Precision Medicine

Cited by 12 publications

References 124 publications

Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways

Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association

New clinical trial design in precision medicine: discovery, development and direction

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