{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:05:58Z","timestamp":1791353158265,"version":"4.3.1"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["MO 3373\/1-1"],"award-info":[{"award-number":["MO 3373\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SFB1002"],"award-info":[{"award-number":["SFB1002"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["F\/63\/21"],"award-info":[{"award-number":["F\/63\/21"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Heart Foundation\/German Foundation of Heart Research","award":["MO 3373\/1-1"],"award-info":[{"award-number":["MO 3373\/1-1"]}]},{"name":"German Heart Foundation\/German Foundation of Heart Research","award":["SFB1002"],"award-info":[{"award-number":["SFB1002"]}]},{"name":"German Heart Foundation\/German Foundation of Heart Research","award":["F\/63\/21"],"award-info":[{"award-number":["F\/63\/21"]}]},{"name":"University Medical Center","award":["MO 3373\/1-1"],"award-info":[{"award-number":["MO 3373\/1-1"]}]},{"name":"University Medical Center","award":["SFB1002"],"award-info":[{"award-number":["SFB1002"]}]},{"name":"University Medical Center","award":["F\/63\/21"],"award-info":[{"award-number":["F\/63\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Left ventricular (LV) dilatation, a prominent risk factor for heart failure (HF), precedes functional deterioration and is used to stratify patients at risk for arrhythmias and cardiac mortality. Aberrant DNA methylation contributes to maladaptive cardiac remodeling and HF progression following pressure overload and ischemic cardiac insults. However, no study has examined cardiac DNA methylation upon exposure to volume overload (VO) despite being relatively common among HF patients. We carried out global methylome analysis of LV harvested at a decompensated HF stage following exposure to VO induced by aortocaval shunt. VO resulted in pathological cardiac remodeling, characterized by massive LV dilatation and contractile dysfunction at 16 weeks after shunt. Although methylated DNA was not markedly altered globally, 25 differentially methylated promoter regions (DMRs) were identified in shunt vs. sham hearts (20 hypermethylated and 5 hypomethylated regions). The validated hypermethylated loci in Junctophilin-2 (Jph2), Signal peptidase complex subunit 3 (Spcs3), Vesicle-associated membrane protein-associated protein B (Vapb), and Inositol polyphosphate multikinase (Ipmk) were associated with the respective downregulated expression and were consistently observed in dilated LV early after shunt at 1 week after shunt, before functional deterioration starts to manifest. These hypermethylated loci were also detected peripherally in the blood of the shunt mice. Altogether, we have identified conserved DMRs that could be novel epigenetic biomarkers in dilated LV upon VO exposure.<\/jats:p>","DOI":"10.3390\/ijms24065885","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T03:15:03Z","timestamp":1679368503000},"page":"5885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["DNA Methylation Analysis Identifies Novel Epigenetic Loci in Dilated Murine Heart upon Exposure to Volume Overload"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8249-5507","authenticated-orcid":false,"given":"Xingbo","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar","family":"Elkenani","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 37075 G\u00f6ttingen, Germany"},{"name":"Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Tan","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), 37075 G\u00f6ttingen, Germany"},{"name":"Department of Nephrology and Rheumatology, University Medical Center of G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jara katharina","family":"Hain","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolong","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-8347","authenticated-orcid":false,"given":"Moritz","family":"Schnelle","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), 37075 G\u00f6ttingen, Germany"},{"name":"Department of Clinical Chemistry, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Hasenfuss","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Toischer","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6705-3241","authenticated-orcid":false,"given":"Belal A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0735-1097(99)00630-0","article-title":"Cardiac remodeling\u2014Concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. 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