Emerging topic: Flow-related epigenetic regulation of endothelial phenotype through DNA methylation

Davies, Peter F.; Manduchi, Elisabetta; Stoeckert, Christian J.; Jiménez, Juan M.; Jiang, Yi‐Zhou

doi:10.1016/j.vph.2014.05.007

Cited by 17 publications

(17 citation statements)

References 51 publications

(58 reference statements)

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“…Several studies have found evidence of epigenetic changes that alter cardiometabolic disease risk, [139][140][141] including defects in endothelial cell function, abnormal blood flow, inflammation, and plaque formation. [142][143][144][145][146][147] Identification and characterization of common epigenetic outcomes linked to disease manifestations and their interaction with nutrient status may allow the development of specific treatment and intervention measures. [148][149][150][151] Interestingly, the effect of limited or oversaturated nutrient bioavailability on epigenetic states is complex and not necessarily direct.…”

Section: Role Of Nutrition In Epigenetic Perturbationmentioning

confidence: 99%

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Ferguson¹,

Allayee²,

Gerszten³

et al. 2016

Circ Cardiovasc Genet

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Abstract-Cardiometabolic diseases are the leading cause of death worldwide and are strongly linked to both genetic and nutritional factors. The field of nutrigenomics encompasses multiple approaches aimed at understanding the effects of diet on health or disease development, including nutrigenetic studies investigating the relationship between genetic variants and diet in modulating cardiometabolic risk, as well as the effects of dietary components on multiple "omic" measures, including transcriptomics, metabolomics, proteomics, lipidomics, epigenetic modifications, and the microbiome. Here, we describe the current state of the field of nutrigenomics with respect to cardiometabolic disease research and outline a direction for the integration of multiple omics techniques in future nutrigenomic studies aimed at understanding mechanisms and developing new therapeutic options for cardiometabolic disease treatment and prevention. The interpretation and scope of nutrigenomics may vary, but it can be thought to encompass the spectrum of nutritional genomics research, including classic nutrigenetics studies of gene-diet interactions and molecular nutrition, in vitro and in vivo models, human nutrition studies, and the application of largescale, unbiased studies using high-throughput "omics" techniques to study the effects of nutrients on the body. 6 As the Figure shows, diet and the genome may influence cardiometabolic health through a variety of interconnected intermediates, perturbations in which can be measured through omics technologies, including RNA expression (transcriptome), epigenetic modifications (epigenome), metabolites (metabolome), lipids (lipidome), proteins (proteome), and resident microbial communities (microbiome). Although it is clear that both nutrients and genes play a distinct role in determining health, the complex interactions among genes, diet, and downstream networks are not well understood. The application of nutrigenomics approaches to questions of human health and disease is an important component in understanding the complexities of the interplay between basic metabolic processes and externalThe American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 22, 2016, and the American Heart Association Executive Committee on February 23, 2016. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The...

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Section: Role Of Nutrition In Epigenetic Perturbationmentioning

confidence: 99%

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Ferguson¹,

Allayee²,

Gerszten³

et al. 2016

Circ Cardiovasc Genet

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“…While it was realized a decade ago that epigenetic/epigenomic pathways can regulate endothelial responses to shear stress, only relatively recently has the emergence of ENCODE and the Human Epigenome Consortium revealed the vast potential of dynamic epigenomic regulation of gene expression, including that by physical stimuli such as biomechanical stress. The recent demonstrations of endothelial KLF4 and HOXA5 proximal promoter DNA hypermethylation by disturbed flow are an emerging epigenomic mechanism 69 of flow-associated transcriptional regulation to add to posttranscriptional regulation by histone remodeling and non-coding RNAs. Further studies will determine if transcriptional regulation by DNA methylation plasticity to flow is common at the many DMRs identified in the endothelial methylome.…”

Section: Perspectivesmentioning

confidence: 99%

Endothelial Epigenetics in Biomechanical Stress

Jiang

Manduchi

Jiménez

et al. 2015

ATVB

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Arterial endothelial phenotype is regulated by local hemodynamic forces that are linked to regional susceptibility to atherogenesis. A complex hierarchy of transcriptional, translational and posttranslational mechanisms are greatly influenced by the characteristics of local arterial shear stress environments. We discuss the emerging role of localized disturbed blood flow upon epigenetic mechanisms of endothelial responses to biomechanical stress, including transcriptional regulation by proximal promoter DNA methylation, and posttranscriptional and translational regulation of gene and protein expression by chromatin remodeling and noncoding RNA-based mechanisms. Dynamic responses to flow characteristics in vivo and in vitro include site-specific differentially methylated regions of swine and mouse endothelial methylomes, histone marks regulating chromatin conformation, microRNAs and long noncoding RNAs. Flow-mediated epigenomic responses intersect with cis and trans factor regulation to maintain endothelial function in a shear-stressed environment and may contribute to localized endothelial dysfunctions that promote atherosusceptibility.

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“…Three active mammalian methyltransferases DNMT1, 3A and 3B promote methylation which is reversed by DNA demethylation through the TET (tet methylcytosine dioxygenase) gene pathway. Flow-induced changes in DNMT1 and 3A have recently been reported (Davies et al 2014; Dunn et al 2014; Jiang et al 2014, 2015b; Zhou et al 2011). DNMT1 is primarily a maintenance enzyme to ensure fidelity of methylation patterns during somatic cell division whereas DNMT3A and 3B regulate de novo DNA methylation.…”

Section: Dna Methylationmentioning

confidence: 90%

“…Thus dynamic DNA methylation appears to be a genome-wide epigenetic mechanism of transcriptional control related to the local site-specific biomechanical stresses of flow. Furthermore, disturbed flow promoted DNA hypermethylation that resulted in transcriptional suppression in human endothelial cells in culture (Davies et al 2014; Dunn et al 2014; Jiang et al 2014, 2015a). Collectively these studies in pigs and mice and cultured cells identified endothelial genes and their promoters as DMR-sensitive epigenomic targets associated with site-specific disturbed flow.…”

Section: Dna Methylationmentioning

confidence: 99%

“…Other epigenetic pathways, however, that regulate chromatin structure are now identified with flow-mediated transcription. Here we introduce epigenetic mechanisms to a readership that may be less familiar with the emerging roles of biofluids and biomechanics in epigenetics, particularly in cardiovascular research, and outline the influence of cell epigenetic status including its plasticity in the regulation of endothelial transcription in flow-sensitive environments (Jiang et al 2014; Davies et al 2014; Dunn et al 2014). …”

Section: Introductionmentioning

confidence: 99%

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Biofluids, cell mechanics and epigenetics: Flow-induced epigenetic mechanisms of endothelial gene expression

Davies

Manduchi

Jiménez

et al. 2017

Journal of Biomechanics

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Epigenetics is the regulation of gene expression (transcription) in response to changes in the cell environment through genomic modifications that largely involve the non-coding fraction of the human genome and that cannot be attributed to modification of the primary DNA sequence. Epigenetics is dominant in establishing cell fate and positioning during programmed embryonic development. However the same pathways are used by mature postnatal and adult mammalian cells during normal physiology and are implicated in disease mechanisms. Recent research demonstrates that blood flow and pressure are cell environments that can influence transcription via epigenetic pathways. The principal epigenetic pathways are chemical modification of cytosine residues of DNA (DNA methylation) and of the amino tails of histone proteins associated with DNA in nucleosomes. They also encompass the post-transcriptional degradation of mRNA transcripts by non-coding RNAs (ncRNA). In vascular endothelium, epigenetic pathways respond to temporal and spatial variations of flow and pressure, particularly hemodynamic disturbed blood flow, with important consequences for gene expression. The biofluid environment is linked by mechanotransduction and solute transport to cardiovascular cell phenotypes via signaling pathways and epigenetic regulation for which there is an adequate interdisciplinary infrastructure with robust tools and methods available. Epigenetic mechanisms may be less familiar than acute genomic signaling to Investigators at the interface of biofluids, biomechanics and cardiovascular biology. Here we introduce a biofluids / cellular biomechanics readership to the principal epigenetic pathways and provide a contextual overview of endothelial epigenetic plasticity in the regulation of flow-responsive transcription.

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Emerging topic: Flow-related epigenetic regulation of endothelial phenotype through DNA methylation

Cited by 17 publications

References 51 publications

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Endothelial Epigenetics in Biomechanical Stress

Biofluids, cell mechanics and epigenetics: Flow-induced epigenetic mechanisms of endothelial gene expression

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