IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-03-04 DOI: 10.1080/15592294.2025.2471127

Mark Hieromnimon, Daniel P Regan, R Peter Lokken, Lawrence B Schook, Ron C Gaba, Kyle M Schachtschneider

{"title":"Single and multi-omic characterization of a porcine model of ethanol-induced hepatic fibrosis.","authors":"Mark Hieromnimon, Daniel P Regan, R Peter Lokken, Lawrence B Schook, Ron C Gaba, Kyle M Schachtschneider","doi":"10.1080/15592294.2025.2471127","DOIUrl":"10.1080/15592294.2025.2471127","url":null,"abstract":"Cirrhosis is a form of end-stage liver disease characterized by extensive hepatic fibrosis and loss of liver parenchyma. It is most commonly the result of long-term alcohol abuse in the United States. Large animal models of cirrhosis, as well as of one of its common long-term sequelae, HCC, are needed to study novel and emerging therapeutic interventions. In the present study, liver fibrosis was induced in the Oncopig cancer model, a large animal HCC model, via intrahepatic, intra-arterial ethanol infusion. Liver sections from five fibrosis induced and five age-matched controls were harvested for RNA-seq (mRNA and lncRNA), small RNA-seq (miRNA), and reduced representation bisulfite sequencing (RRBS; DNA methylation). Single- and multi-omic analysis was performed to investigate the transcriptomic and epigenomic mechanisms associated with fibrosis deposition in this model. A total of 3,439 genes, 70 miRNAs, 452 lncRNAs, and 7,715 methylation regions were found to be differentially regulated through individual single-omic analysis. Pathway analysis indicated differentially expressed genes were associated with collagen synthesis and turnover, hepatic metabolic functions such as ethanol and lipid metabolism, and proliferative and anti-proliferative pathways including PI3K and BAX/BCL signaling pathways. Multi-omic latent variable analysis demonstrated significant concordance with the single-omic analysis. lncRNA's associated with UHRF1BP1L and S1PR1 genes were found to reliably discriminate the two arms of the study. These genes were previously implicated in human cancer development and vasculogenesis, respectively. These findings support the validity and translatability of this model as a useful preclinical tool in the study of alcoholic liver disease and its treatment.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2471127"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astrocyte-derived exosomes regulate sperm miR-34c levels to mediate the transgenerational effects of paternal chronic social instability stress. 星形胶质细胞衍生的外泌体调节精子miR-34c水平，介导父亲慢性社会不稳定压力的跨代效应。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-01-27 DOI: 10.1080/15592294.2025.2457176

Alexandre Champroux, Mitra Sadat-Shirazi, Xuan Chen, Jonathan Hacker, Yongjie Yang, Larry A Feig

{"title":"Astrocyte-derived exosomes regulate sperm miR-34c levels to mediate the transgenerational effects of paternal chronic social instability stress.","authors":"Alexandre Champroux, Mitra Sadat-Shirazi, Xuan Chen, Jonathan Hacker, Yongjie Yang, Larry A Feig","doi":"10.1080/15592294.2025.2457176","DOIUrl":"10.1080/15592294.2025.2457176","url":null,"abstract":"The effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content, which induce stress-specific phenotypes in their offspring. However, how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not known. We showed previously that exposure of male mice to chronic social instability (CSI) stress results in elevated anxiety and reduced sociability specifically in their female offspring across multiple generations because it reduces miR-34c levels in sperm of stressed males and their unstressed male offspring. Here, we describe evidence that astrocyte-derived exosomes (A-Exos) carrying miR-34c mediate how CSI stress has this transgenerational effect on sperm. We found that CSI stress decreases miR-34c carried by A-Exos in the prefrontal cortex and amygdala, as well as in the blood of males. Importantly, miR-34c A-Exos levels are also reduced in these tissues in their F1 male offspring, who despite not being exposed to stress, exhibit reduced sperm miR-34c levels and transmit the same stress-associated traits to their male and female offspring. Furthermore, restoring A-Exos miR-34c content in the blood of CSI-stressed males by intravenous injection of miR-34c-containing A-Exos restores miR-34c levels in their sperm. These findings reveal an unexpected role for A-Exos in maintaining sperm miR-34c levels by a process that when suppressed by CSI stress mediates this example of transgenerational epigenetic inheritance.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2457176"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines. α -亚麻酸介导的宫颈癌细胞系表观遗传重编程。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-02 DOI: 10.1080/15592294.2025.2451551

Amrita Ulhe, Prerna Raina, Amol Chaudhary, Ruchika Kaul-Ghanekar

{"title":"Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines.","authors":"Amrita Ulhe, Prerna Raina, Amol Chaudhary, Ruchika Kaul-Ghanekar","doi":"10.1080/15592294.2025.2451551","DOIUrl":"10.1080/15592294.2025.2451551","url":null,"abstract":"Cervical cancer, the fourth most common cancer globally and the second most prevalent cancer among women in India, is primarily caused by Human Papilloma Virus (HPV). The association of diet with cancer etiology and prevention has been well established and nutrition has been shown to regulate cancer through modulation of epigenetic markers. Dietary fatty acids, especially omega-3, reduce the risk of cancer by preventing or reversing the progression through a variety of cellular targets, including epigenetic regulation. In this work, we have evaluated the potential of ALA (α linolenic acid), an ω-3 fatty acid, to regulate cervical cancer through epigenetic mechanisms. The effect of ALA was evaluated on the regulation of histone deacetylases1, DNA methyltransferases 1, and 3b, and global DNA methylation by ELISA. RT-PCR was utilized to assess the expression of tumor regulatory genes (hTERT, DAPK, RARβ, and CDH1) and their promoter methylation in HeLa (HPV18-positive), SiHa (HPV16-positive) and C33a (HPV-negative) cervical cancer cell lines. ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines. ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines. ALA reduced methylation in the 5' CpG island of CDH1, RARβ, and DAPK1 promoters and reduced global DNA methylation in cervical cancer cell lines. These results suggest that ALA regulates the growth of cervical cancer cells by targeting epigenetic markers, shedding light on its potential therapeutic role in cervical cancer management.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2451551"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blood transcriptomic associations of epigenetic age in adolescents. 青少年表观遗传年龄的血液转录组学关联。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-16 DOI: 10.1080/15592294.2025.2503824

Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas

{"title":"Blood transcriptomic associations of epigenetic age in adolescents.","authors":"Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas","doi":"10.1080/15592294.2025.2503824","DOIUrl":"10.1080/15592294.2025.2503824","url":null,"abstract":"Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14-15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the limma-voom pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of MYO6 and ZBTB38 across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40-54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2503824"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. 脐带血甲基化差异模式与产前暴露于社区犯罪相关：一项全表观基因组关联研究和区域分析。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-06-10 DOI: 10.1080/15592294.2025.2511553

Chantel L Martin, Jiawen Chen, Alena S D'Alessio, Cavin K Ward-Caviness, Ai Ye, Evans K Lodge, Lea Ghastine, Radhika Dhingra, Dereje D Jima, Susan K Murphy, Cathrine Hoyo

{"title":"Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis.","authors":"Chantel L Martin, Jiawen Chen, Alena S D'Alessio, Cavin K Ward-Caviness, Ai Ye, Evans K Lodge, Lea Ghastine, Radhika Dhingra, Dereje D Jima, Susan K Murphy, Cathrine Hoyo","doi":"10.1080/15592294.2025.2511553","DOIUrl":"10.1080/15592294.2025.2511553","url":null,"abstract":"Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2511553"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Poly-epigenetic scores for cardiometabolic risk factors interact with demographic factors and health behaviors in older US Adults. 美国老年人心脏代谢危险因素的多表观遗传评分与人口统计学因素和健康行为的相互作用

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/15592294.2025.2469205

Lisha Lin, Wei Zhao, Zheng Li, Scott M Ratliff, Yi Zhe Wang, Colter Mitchell, Jessica D Faul, Sharon L R Kardia, Kira S Birditt, Jennifer A Smith

{"title":"Poly-epigenetic scores for cardiometabolic risk factors interact with demographic factors and health behaviors in older US Adults.","authors":"Lisha Lin, Wei Zhao, Zheng Li, Scott M Ratliff, Yi Zhe Wang, Colter Mitchell, Jessica D Faul, Sharon L R Kardia, Kira S Birditt, Jennifer A Smith","doi":"10.1080/15592294.2025.2469205","DOIUrl":"10.1080/15592294.2025.2469205","url":null,"abstract":"Poly-epigenetic scores (PEGS) are surrogate measures that help capture individual-level risk. Understanding how the associations between PEGS and cardiometabolic risk factors vary by demographics and health behaviors is crucial for lowering the burden of cardiometabolic diseases. We used results from established epigenome-wide association studies to construct trait-specific PEGS from whole blood DNA methylation for systolic and diastolic blood pressure (SBP, DBP), body mass index (BMI), C-reactive protein (CRP), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), triglycerides (TG), and fasting glucose. Overall and race-stratified associations between PEGS and corresponding traits were examined in adults >50 years from the Health and Retirement Study (n = 3,996, mean age = 79.5 years). We investigated how demographics (age, sex, educational attainment) and health behaviors (smoking, alcohol consumption, physical activity) modified these associations. All PEGS were positively associated with their corresponding cardiometabolic traits (p < 0.05), and most associations persisted across all racial/ethnic groups. Associations for BMI, HDL-C, and TG were stronger in younger participants, and BMI and HDL-C associations were stronger in females. The CRP association was stronger among those with a high school degree. Finally, the HDL-C association was stronger among current smokers. These findings support PEGS as robust surrogate measures and suggest the associations may differ among subgroups.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2469205"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Normal bronchial field basal cells show persistent methylome-wide impact of tobacco smoking, including in known cancer genes. 正常支气管野基底细胞显示吸烟对甲基组的持续影响，包括已知的癌症基因。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/15592294.2025.2466382

Batbayar Khulan, Kenny Ye, Miao Kevin Shi, Spencer Waldman, Ava Marsh, Taha Siddiqui, Aham Okorozo, Aditi Desai, Dhruv Patel, Jay Dobkin, Ali Sadoughi, Chirag Shah, Shweta Gera, Yakov Peter, Will Liao, Jan Vijg, Simon D Spivack

{"title":"Normal bronchial field basal cells show persistent methylome-wide impact of tobacco smoking, including in known cancer genes.","authors":"Batbayar Khulan, Kenny Ye, Miao Kevin Shi, Spencer Waldman, Ava Marsh, Taha Siddiqui, Aham Okorozo, Aditi Desai, Dhruv Patel, Jay Dobkin, Ali Sadoughi, Chirag Shah, Shweta Gera, Yakov Peter, Will Liao, Jan Vijg, Simon D Spivack","doi":"10.1080/15592294.2025.2466382","DOIUrl":"10.1080/15592294.2025.2466382","url":null,"abstract":"Lung carcinogenesis is causally linked to cigarette smoking, in part by epigenetic changes. We tested whether accumulated epigenetic change in smokers is apparent in bronchial basal cells as cells of origin of squamous cell carcinoma. Using an EM-seq platform covering 53.8 million CpGs (96% of the entire genome) at an average of 7.5 sequencing reads per CpG site at a single base resolution, we evaluated cytology-normal basal cells bronchoscopically brushed from the in situ tobacco smoke-exposed 'bronchial epithelial field' and isolated by short-term primary culture from 54 human subjects. We found that mean methylation was globally lower in ever (former and current) smokers versus never smokers (p = 0.0013) across promoters, CpG shores, exons, introns, 3'-UTRs, and intergenic regions, but not in CpG islands. Among 6mers with dinucleotides flanking CpG, those containing CGCG showed no effect from smoking, while those flanked with TT and AA displayed the strongest effects. At the gene level, smoking-related differences in methylation level were observed in CDKL1, ARTN, EDC3, CYP1B1, FAM131A, and MAGI2. Among candidate cancer genes, smoking reduced the methylation level in KRAS, ROS1, CDKN1A, CHRNB4, and CADM1. We conclude that smoking reduces long-term epigenome-wide methylation in bronchial stem cells, is impacted by the flanking sequence, and persists indefinitely beyond smoking cessation.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2466382"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An overview of potential of natural compounds to regulate epigenetic modifications in colorectal cancer: a recent update. 概述了天然化合物调节结肠直肠癌表观遗传修饰的潜力：最近更新。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-04-16 DOI: 10.1080/15592294.2025.2491316

Susmita Roy, Dikshita Deka, Suresh Babu Kondaveeti, Pavithra Ayyadurai, Sravani Siripragada, Neha Philip, Surajit Pathak, Asim K Duttaroy, Antara Banerjee

{"title":"An overview of potential of natural compounds to regulate epigenetic modifications in colorectal cancer: a recent update.","authors":"Susmita Roy, Dikshita Deka, Suresh Babu Kondaveeti, Pavithra Ayyadurai, Sravani Siripragada, Neha Philip, Surajit Pathak, Asim K Duttaroy, Antara Banerjee","doi":"10.1080/15592294.2025.2491316","DOIUrl":"https://doi.org/10.1080/15592294.2025.2491316","url":null,"abstract":"Colorectal cancer (CRC) remains an alarming global health concern despite advancements in treatment modalities over recent decades. Among the various factors contributing to CRC, this review emphasizes the critical role of epigenetic mechanisms in its pathogenesis and progression. This review also describes the potential role of natural compounds in altering the epigenetic landscape, focused mainly on DNA methylation, histone modification, and non-coding RNAs. Publications from the previous five years were searched and retrieved using well-known search engines and databases like PubMed, Google Scholar, and ScienceDirect. Keywords like CRC/colorectal cancer, CAC/Colitis associated CRC, inflammasomes, epigenetic modulation, genistein, curcumin, quercetin, resveratrol, anthocyanins, sulforaphane, and epigallocatechin-3-gallate were used in various combinations during the search. These natural compounds predominantly affect pathways such as Wnt/β-catenin, NF-κB, and PI3K/AKT to suppress CRC cell proliferation and oxidative stress and enhance anti-inflammation and apoptosis. However, their clinical use is restricted due to their low bioavailability. However, multiple methods exist to overcome challenges like this, including but not limited to structural modifications, nanoparticle encapsulations, bio-enhancers, and novel advanced delivery systems. These methods improve their potential as supportive therapies that target CRC progression epigenetically with fewer side effects. Current research focuses on enhancing epigenetic targeting to control CRC progression while minimizing side effects, emphasizing improved specificity, bioavailability, and efficacy as standalone or synergistic therapies.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2491316"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-lasting metabolic impairment in the failing heart: epigenetic memories at play. 衰竭心脏的长期代谢损伤：表观遗传记忆在起作用。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-06-10 DOI: 10.1080/15592294.2025.2515430

Sarah Costantino, Francesco Paneni

{"title":"Long-lasting metabolic impairment in the failing heart: epigenetic memories at play.","authors":"Sarah Costantino, Francesco Paneni","doi":"10.1080/15592294.2025.2515430","DOIUrl":"https://doi.org/10.1080/15592294.2025.2515430","url":null,"abstract":"Understanding the factors involved in myocardial recovery after unloading is of utmost importance to unveil new therapies in patients with heart failure (HF). Lack of myocardial recovery might be explained by long-lasting molecular alterations which persist despite normalization of cardiac stress. In this issue of Epigenetics, Roth et al. present an elegant translational study addressing this important aspect at the molecular level. By leveraging a mouse model of reversible transverse aortic constriction (rTAC) and human LV samples from HF patients undergoing LVAD therapy, the authors show that cardiac unloading is associated with a persistent deregulation of transcriptional programmes implicated in mitochondrial respiration, fatty acid and acyl-CoA metabolism, suggesting a long-lasting metabolic deterioration of the failing heart. Of interest, the authors identified several chromatin remodellers (Hdac4, Smarca2, and Brd4) potentially explaining the observed transcriptional alterations. Taken together, these novel findings suggest that 'DNA forgives but does not forget,' thus leaving an epigenetic scar which hampers the recovery of the failing heart after unloading. Disentangling the epigenetic factors involved in such 'transcriptional memory' may set the stage for new interventions resetting the cardiomyocyte transcriptome and myocardial energetics thus fostering a true myocardial recovery in HF.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2515430"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors. 小鼠和人类心肌细胞恢复的转录特征揭示了表观遗传因子的持续上调。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-06-05 DOI: 10.1080/15592294.2025.2506625

Rebekka Roth, Margareta Häckh, Tilman Schnick, Carolin Rommel, Christoph Koentges, Heiko Bugger, Claudia Domisch, Michael R Bristow, Amrut V Ambardekar, Timothy A McKinsey, Ralf Gilsbach, Lutz Hein, Sebastian Preissl

{"title":"Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors.","authors":"Rebekka Roth, Margareta Häckh, Tilman Schnick, Carolin Rommel, Christoph Koentges, Heiko Bugger, Claudia Domisch, Michael R Bristow, Amrut V Ambardekar, Timothy A McKinsey, Ralf Gilsbach, Lutz Hein, Sebastian Preissl","doi":"10.1080/15592294.2025.2506625","DOIUrl":"10.1080/15592294.2025.2506625","url":null,"abstract":"Fibrosis, cardiac remodelling, and inflammation are hallmarks of heart failure. To date, there is no available pharmacological cure for heart failure, but mechanical unloading by implantation of a left ventricular assist device (LVAD) can lead to improved cardiac function in a subset of patients. This study aimed to identify the transcriptional response of left ventricular (LV) cardiac myocytes to mechanical unloading in a mouse model of reversible LV pressure overload and in failing human hearts after LVAD implantation. We found that partial recovery of ventricular dysfunction, LV hypertrophy, and gene expression programmes occurred in mice under reversible transverse aortic constriction (rTAC). Gene expression analysis in cardiac myocytes identified a lasting repression of mitochondrial gene expression resulting in compromised fatty acid oxidation in the mouse model of reversible pressure overload and in human LV samples after LVAD therapy and a persistent upregulation of epigenetic and transcriptional regulators. These findings underpin that recovery from heart failure involves complex gene regulatory networks and that mitochondrial dysfunction remains a challenge even after mechanical unloading. Further studies are needed to investigate the functional role of these factors in reverse remodelling and recovery of failing hearts.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2506625"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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