High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction
Novel biomarkers are needed to better identify-and distinguish-heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented ge...
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| creator | Benincasa, Giuditta Pepin, Mark E Russo, Vincenzo Cacciatore, Francesco D'Alto, Michele Argiento, Paola Romeo, Emanuele Chiappetti, Rosaria Laezza, Nunzia Wende, Adam R Schiattarella, Gabriele G Coscioni, Enrico La Montagna, Antonietta Amarelli, Cristiano Maiello, Ciro Golino, Paolo Condorelli, Gianluigi Napoli, Claudio |
| description | Novel biomarkers are needed to better identify-and distinguish-heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4
T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.e., discovery/validation) each of both male and female patients with HFpEF (n = 12/10), HF with reduced EF (HFrEF; n = 7/5), and volunteers lacking clinical evidence of HF (CON; n = 7/5). RRBS is the gold-standard platform for measuring genome-wide DNA methylation changes at single-cytosine resolution in hypothesis-generating studies. We identified three hypomethylated HFpEF-specific differentially methylated positions (DMPs) associated with FOXB1, ELMOD1, and DGKH genes wherein ROC curve analysis revealed that increased expression levels had a reasonable diagnostic performance in predicting HFpEF (AUC ≥ 0.8, p |
| doi_str_mv | 10.1007/s00395-024-01093-7 |
| format | Article |
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T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.e., discovery/validation) each of both male and female patients with HFpEF (n = 12/10), HF with reduced EF (HFrEF; n = 7/5), and volunteers lacking clinical evidence of HF (CON; n = 7/5). RRBS is the gold-standard platform for measuring genome-wide DNA methylation changes at single-cytosine resolution in hypothesis-generating studies. We identified three hypomethylated HFpEF-specific differentially methylated positions (DMPs) associated with FOXB1, ELMOD1, and DGKH genes wherein ROC curve analysis revealed that increased expression levels had a reasonable diagnostic performance in predicting HFpEF (AUC ≥ 0.8, p < 0.05). Network analysis identified additional three genes including JUNB (p = 0.037), SETD7 (p = 0.003), and MEF2D (p = 0.0001) which were significantly higher in HFpEF vs. HFrEF patients. ROC curve analysis showed that integrating the functional H
FPEF classification with the expression levels of the FOXB1, ELMOD1, and DGKH as well as the JUNB, SETD7, and MEF2D genes improved diagnostic accuracy, with AUC = 0.8 (p < 0.0001) as compared to H
FPEF score alone (p > 0.05). Besides, increased expression levels of SETD7-RELA-IL6 axis significantly discriminated overweight/obese HFpEF vs. HFrEF patients (AUC = 1; p = 0.001, p = 0.006, p = 0.006, respectively). We support an emerging dogma that indirect epigenetic testing via high-resolution RRBS methylomics represents a non-invasive tool that may enable easier access to both diagnostic and mechanistic insights of HFpEF. An epigenetic-oriented dysregulation of network-derived SETD7-RELA-IL6 axis in circulating CD4
T lymphocytes may drive pro-inflammatory responses which, in turn, may lead to cardiac remodeling in overweight/obese HFpEF.</description><identifier>ISSN: 1435-1803</identifier><identifier>EISSN: 1435-1803</identifier><identifier>DOI: 10.1007/s00395-024-01093-7</identifier><identifier>PMID: 39725721</identifier><language>eng</language><publisher>Germany</publisher><ispartof>Basic research in cardiology, 2024-12</ispartof><rights>2024. Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c184t-c2138aa6f8804f7495dd50d1ad054b33a4d9428e9c23feaf80db0a43012d6a833</cites><orcidid>0000-0002-7552-3522</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39725721$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Benincasa, Giuditta</creatorcontrib><creatorcontrib>Pepin, Mark E</creatorcontrib><creatorcontrib>Russo, Vincenzo</creatorcontrib><creatorcontrib>Cacciatore, Francesco</creatorcontrib><creatorcontrib>D'Alto, Michele</creatorcontrib><creatorcontrib>Argiento, Paola</creatorcontrib><creatorcontrib>Romeo, Emanuele</creatorcontrib><creatorcontrib>Chiappetti, Rosaria</creatorcontrib><creatorcontrib>Laezza, Nunzia</creatorcontrib><creatorcontrib>Wende, Adam R</creatorcontrib><creatorcontrib>Schiattarella, Gabriele G</creatorcontrib><creatorcontrib>Coscioni, Enrico</creatorcontrib><creatorcontrib>La Montagna, Antonietta</creatorcontrib><creatorcontrib>Amarelli, Cristiano</creatorcontrib><creatorcontrib>Maiello, Ciro</creatorcontrib><creatorcontrib>Golino, Paolo</creatorcontrib><creatorcontrib>Condorelli, Gianluigi</creatorcontrib><creatorcontrib>Napoli, Claudio</creatorcontrib><title>High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction</title><title>Basic research in cardiology</title><addtitle>Basic Res Cardiol</addtitle><description>Novel biomarkers are needed to better identify-and distinguish-heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4
T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.e., discovery/validation) each of both male and female patients with HFpEF (n = 12/10), HF with reduced EF (HFrEF; n = 7/5), and volunteers lacking clinical evidence of HF (CON; n = 7/5). RRBS is the gold-standard platform for measuring genome-wide DNA methylation changes at single-cytosine resolution in hypothesis-generating studies. We identified three hypomethylated HFpEF-specific differentially methylated positions (DMPs) associated with FOXB1, ELMOD1, and DGKH genes wherein ROC curve analysis revealed that increased expression levels had a reasonable diagnostic performance in predicting HFpEF (AUC ≥ 0.8, p < 0.05). Network analysis identified additional three genes including JUNB (p = 0.037), SETD7 (p = 0.003), and MEF2D (p = 0.0001) which were significantly higher in HFpEF vs. HFrEF patients. ROC curve analysis showed that integrating the functional H
FPEF classification with the expression levels of the FOXB1, ELMOD1, and DGKH as well as the JUNB, SETD7, and MEF2D genes improved diagnostic accuracy, with AUC = 0.8 (p < 0.0001) as compared to H
FPEF score alone (p > 0.05). Besides, increased expression levels of SETD7-RELA-IL6 axis significantly discriminated overweight/obese HFpEF vs. HFrEF patients (AUC = 1; p = 0.001, p = 0.006, p = 0.006, respectively). We support an emerging dogma that indirect epigenetic testing via high-resolution RRBS methylomics represents a non-invasive tool that may enable easier access to both diagnostic and mechanistic insights of HFpEF. An epigenetic-oriented dysregulation of network-derived SETD7-RELA-IL6 axis in circulating CD4
T lymphocytes may drive pro-inflammatory responses which, in turn, may lead to cardiac remodeling in overweight/obese HFpEF.</description><issn>1435-1803</issn><issn>1435-1803</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNptkbtOw0AURFcIRELgByjQljSGuw-_yig8ghRBA_Vq7b0bOzhx2LWD8g98NE4cEAXVnSvNnGKGkEsGNwwgvvUAIg0D4DIABqkI4iMyZFKEAUtAHP_RA3Lm_QKAyShip2Qg0piHMWdD8jUt50Xg0NdV25T1it49j-kSm2Jb6f2fF3o1R08dblBXNCvrpXbv6DytLS1Qu4ZaXVatQ_pZNgVddyx0GzQUF5jvEdbpXmy6WLtDmTb_z3BOTqyuPF4c7oi8Pdy_TqbB7OXxaTKeBTlLZBPknIlE68gmCUgbyzQ0JgTDtIFQZkJoaVLJE0xzLixqm4DJQEsBjJtIJ0KMyHXPXbv6o0XfqGXpc6wqvcK69UqwjimFFLyz8t6au9p7h1atXdk1sFUM1G4F1a-guhXUfgUVd6GrA7_Nlmh-Iz-1i29SQIXr</recordid><startdate>20241227</startdate><enddate>20241227</enddate><creator>Benincasa, Giuditta</creator><creator>Pepin, Mark E</creator><creator>Russo, Vincenzo</creator><creator>Cacciatore, Francesco</creator><creator>D'Alto, Michele</creator><creator>Argiento, Paola</creator><creator>Romeo, Emanuele</creator><creator>Chiappetti, Rosaria</creator><creator>Laezza, Nunzia</creator><creator>Wende, Adam R</creator><creator>Schiattarella, Gabriele G</creator><creator>Coscioni, Enrico</creator><creator>La Montagna, Antonietta</creator><creator>Amarelli, Cristiano</creator><creator>Maiello, Ciro</creator><creator>Golino, Paolo</creator><creator>Condorelli, Gianluigi</creator><creator>Napoli, Claudio</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7552-3522</orcidid></search><sort><creationdate>20241227</creationdate><title>High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction</title><author>Benincasa, Giuditta ; Pepin, Mark E ; Russo, Vincenzo ; Cacciatore, Francesco ; D'Alto, Michele ; Argiento, Paola ; Romeo, Emanuele ; Chiappetti, Rosaria ; Laezza, Nunzia ; Wende, Adam R ; Schiattarella, Gabriele G ; Coscioni, Enrico ; La Montagna, Antonietta ; Amarelli, Cristiano ; Maiello, Ciro ; Golino, Paolo ; Condorelli, Gianluigi ; Napoli, Claudio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c184t-c2138aa6f8804f7495dd50d1ad054b33a4d9428e9c23feaf80db0a43012d6a833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Benincasa, Giuditta</creatorcontrib><creatorcontrib>Pepin, Mark E</creatorcontrib><creatorcontrib>Russo, Vincenzo</creatorcontrib><creatorcontrib>Cacciatore, Francesco</creatorcontrib><creatorcontrib>D'Alto, Michele</creatorcontrib><creatorcontrib>Argiento, Paola</creatorcontrib><creatorcontrib>Romeo, Emanuele</creatorcontrib><creatorcontrib>Chiappetti, Rosaria</creatorcontrib><creatorcontrib>Laezza, Nunzia</creatorcontrib><creatorcontrib>Wende, Adam R</creatorcontrib><creatorcontrib>Schiattarella, Gabriele G</creatorcontrib><creatorcontrib>Coscioni, Enrico</creatorcontrib><creatorcontrib>La Montagna, Antonietta</creatorcontrib><creatorcontrib>Amarelli, Cristiano</creatorcontrib><creatorcontrib>Maiello, Ciro</creatorcontrib><creatorcontrib>Golino, Paolo</creatorcontrib><creatorcontrib>Condorelli, Gianluigi</creatorcontrib><creatorcontrib>Napoli, Claudio</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Basic research in cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Benincasa, Giuditta</au><au>Pepin, Mark E</au><au>Russo, Vincenzo</au><au>Cacciatore, Francesco</au><au>D'Alto, Michele</au><au>Argiento, Paola</au><au>Romeo, Emanuele</au><au>Chiappetti, Rosaria</au><au>Laezza, Nunzia</au><au>Wende, Adam R</au><au>Schiattarella, Gabriele G</au><au>Coscioni, Enrico</au><au>La Montagna, Antonietta</au><au>Amarelli, Cristiano</au><au>Maiello, Ciro</au><au>Golino, Paolo</au><au>Condorelli, Gianluigi</au><au>Napoli, Claudio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction</atitle><jtitle>Basic research in cardiology</jtitle><addtitle>Basic Res Cardiol</addtitle><date>2024-12-27</date><risdate>2024</risdate><issn>1435-1803</issn><eissn>1435-1803</eissn><abstract>Novel biomarkers are needed to better identify-and distinguish-heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4
T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.e., discovery/validation) each of both male and female patients with HFpEF (n = 12/10), HF with reduced EF (HFrEF; n = 7/5), and volunteers lacking clinical evidence of HF (CON; n = 7/5). RRBS is the gold-standard platform for measuring genome-wide DNA methylation changes at single-cytosine resolution in hypothesis-generating studies. We identified three hypomethylated HFpEF-specific differentially methylated positions (DMPs) associated with FOXB1, ELMOD1, and DGKH genes wherein ROC curve analysis revealed that increased expression levels had a reasonable diagnostic performance in predicting HFpEF (AUC ≥ 0.8, p < 0.05). Network analysis identified additional three genes including JUNB (p = 0.037), SETD7 (p = 0.003), and MEF2D (p = 0.0001) which were significantly higher in HFpEF vs. HFrEF patients. ROC curve analysis showed that integrating the functional H
FPEF classification with the expression levels of the FOXB1, ELMOD1, and DGKH as well as the JUNB, SETD7, and MEF2D genes improved diagnostic accuracy, with AUC = 0.8 (p < 0.0001) as compared to H
FPEF score alone (p > 0.05). Besides, increased expression levels of SETD7-RELA-IL6 axis significantly discriminated overweight/obese HFpEF vs. HFrEF patients (AUC = 1; p = 0.001, p = 0.006, p = 0.006, respectively). We support an emerging dogma that indirect epigenetic testing via high-resolution RRBS methylomics represents a non-invasive tool that may enable easier access to both diagnostic and mechanistic insights of HFpEF. An epigenetic-oriented dysregulation of network-derived SETD7-RELA-IL6 axis in circulating CD4
T lymphocytes may drive pro-inflammatory responses which, in turn, may lead to cardiac remodeling in overweight/obese HFpEF.</abstract><cop>Germany</cop><pmid>39725721</pmid><doi>10.1007/s00395-024-01093-7</doi><orcidid>https://orcid.org/0000-0002-7552-3522</orcidid></addata></record> |
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| title | High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction |
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