Epigenetic Network in Immunometabolic Disease

Geiger, Martin; Gorica, Era; Mohammed, Shafeeq Ahmed; Mongelli, Alessia; Mengozi, Alessandro; Delfine, Valentina; Ruschitzka, Frank; Costantino, Sarah; Paneni, Francesco

doi:10.1002/adbi.202300211

Cited by 3 publications

(2 citation statements)

References 228 publications

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“…It is worth to cite the potential impact of epigenetics to the pathogenesis of human diseases [57][58][59]. Currently, the role of control of gene expression by non-coding RNAs is a hot topic of research including cardiovascular diseases [60][61][62].…”

Section: Discussionmentioning

confidence: 99%

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

Alves de Oliveira,

de Menezes Neves,

de Figueiredo Oliveira

et al. 2024

PLoS ONE

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Atherosclerotic Cardiovascular Disease (ASCVD) represents the leading cause of death worldwide, and individual screening should be based on behavioral, metabolic, and genetic profile derived from data collected in large population-based studies. Due to the polygenic nature of ASCVD, we aimed to assess the association of genomics with ASCVD risk and its impact on the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events at population level. CardioVascular Genes (CV-GENES) is a nationwide, multicenter, 1:1 case-control study of 3,734 patients in Brazil. Inclusion criterion for cases is the first occurrence of one of the ASCVD events. Individuals without known ASCVD will be eligible as controls. A core lab will perform the genetic analyses through low-pass whole genome sequencing and whole exome sequencing. In order to estimate the independent association between genetic polymorphisms and ASCVD, a polygenic risk score (PRS) will be built through a hybrid approach including effect size of each Single Nucleotide Polymorphism (SNP), number of effect alleles observed, sample ploidy, total number of SNPs included in the PRS, and number of non-missing SNPs in the sample. In addition, the presence of pathogenic or likely pathogenic variants will be screened in 8 genes (ABCG5, ABCG8, APOB, APOE, LDLR, LDLRAP1, LIPA, PCSK9) associated with atherosclerosis. Multiple logistic regression will be applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI), and population attributable risks will be calculated. Clinical trial registration: This study is registered in clinicaltrials.gov (NCT05515653).

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Section: Discussionmentioning

confidence: 99%

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

Alves de Oliveira,

de Menezes Neves,

de Figueiredo Oliveira

et al. 2024

PLoS ONE

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“…Intercellular communication between cardiac fibroblasts and cells in their niche environment integrates information provided by direct mechanical signals, cell-cell contact, and soluble factors such as tissue cytokines, immune cell–derived chemokines and cytokines, and modulators of cellular metabolism. 128 Following activation during tissue injury or inflammation, cardiac fibroblasts undergo substantial changes to support both inflammatory processes and contribute to tissue repair. The outcome of the interaction of cardiac fibroblasts with other cells in their microenvironmental niches is highly dependent on contextual cues.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Fibroblastic Niches in Homeostasis and Inflammation

Cadosch,

Gil-Cruz,

Perez-Shibayama

et al. 2024

Circulation Research

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Fibroblasts are essential for building and maintaining the structural integrity of all organs. Moreover, fibroblasts can acquire an inflammatory phenotype to accommodate immune cells in specific niches and to provide migration, differentiation, and growth factors. In the heart, balancing of fibroblast activity is critical for cardiac homeostasis and optimal organ function during inflammation. Fibroblasts sustain cardiac homeostasis by generating local niche environments that support housekeeping functions and by actively engaging in intercellular cross talk. During inflammatory perturbations, cardiac fibroblasts rapidly switch to an inflammatory state and actively communicate with infiltrating immune cells to orchestrate immune cell migration and activity. Here, we summarize the current knowledge on the molecular landscape of cardiac fibroblasts, focusing on their dual role in promoting tissue homeostasis and modulating immune cell–cardiomyocyte interaction. In addition, we discuss potential future avenues for manipulating cardiac fibroblast activity during myocardial inflammation.

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Aberrant DNA methylation associated with the development of metabolic dysfunction-associated fatty liver disease

Abaturov,

Nikulina,

Rusakova

2024

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The literature review deals with DNA methylation, a key epigenetic mechanism that controls the activity of gene transcription, plays a decisive role in the formation of genomic imprinting, gene silencing, X-chromosome inactivation, RNA splicing, DNA repair, cell differentiation and cell reprogramming, and also determines the occurrence and development of liver steatotic lesions and metabolic disorders. Methylation of DNA cytosine dinucleotide (CpG) can be represented in two types: de novo CpG methylation, which is carried out by 5mC DNA writers — DNA-(cytosine-5)-methyltransferase (DNMT) 3a and 3b, and supporting DNA methylation, which is performed by DNMT1 during DNA replication. It has been found that the maintenance DNA methylation allows the preservation of the methylation pattern characteristic of progenitor cells in the cells of the new generation, and the DNA methylation of the gene body is associated with its increased expression. Active demethylation of 5mC is carried out by TET dioxygenases, including three enzymatic representatives: TET1, TET2 and TET3. It has been demonstrated that aberrant methylation of DNA nucleotides is directly related to the activity of lipid synthesis, the degree of oxidative stress, the development of liver steatosis, low-grade inflammation, insulin resistance, and the progression of liver fibrosis. The authors presented in detail the functions and features of DNA methyltransferases, erasers, and readers of 5mC sites; possible violations of the balance of activity of writers and erasers of 5mC DNA; DNA methylation landscape and patterns; clinical significance of DNA methylation signatures in metabolic dysfunction-associated fatty liver disease. Global hypomethylation of genome, at least 55 genes, is observed in patients with metabolic dysfunction-associated fatty liver disease. The authors emphasize that the use of DNA methylation signatures is a promising direction for early diagnosis and prognosis of the course of metabolic dysfunction-associated fatty liver disease, while the study of molecular components of DNA methylation mechanisms involved in the regulation of gene expression, the dependence of their activity on exposure to the exposome will allow to personalize and improve recommendations for lifestyle and diet modification in patients with metabolic dysfunction-associated fatty liver disease.

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Epigenetic Network in Immunometabolic Disease

Cited by 3 publications

References 228 publications

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil

Cardiac Fibroblastic Niches in Homeostasis and Inflammation

Aberrant DNA methylation associated with the development of metabolic dysfunction-associated fatty liver disease

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