{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:19:57Z","timestamp":1792588797657,"version":"4.5.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The epigenetic mechanisms underlying early-onset acute myocardial infarction (AMI) remain insufficiently characterized. The present study aims to elucidate the pathophysiology of early-onset AMI by investigating its epigenetic features as molecular indicators.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>A comparative differential methylation analysis was performed on whole blood samples from 298 patients with early-onset AMI with clinical follow-up and 247 controls using targeted bisulfite sequencing. Clusters of differentially methylated sites (CDMSs) were defined to highlight regions of concentrated methylation changes in patients with early-onset AMI. Cox proportional hazards regression was conducted to evaluate the prognostic significance of the methylation biomarkers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              A total of 692 differentially methylated sites (DMSs) were identified as biomarkers associated with early-onset AMI. Among these, 396 DMSs were grouped into 147 CDMSs. Notably, the\n              <jats:italic toggle=\"yes\">UHRF1<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">STIMATE<\/jats:italic>\n              genes, which regulate synthetic and osteoblast-like vascular smooth muscle cell phenotypes, respectively, contained CDMSs with the highest number of significant DMSs.\n              <jats:italic toggle=\"yes\">UHRF1<\/jats:italic>\n              demonstrated a CDMS with 10 significant DMSs within a 117-bp region, while\n              <jats:italic toggle=\"yes\">STIMATE<\/jats:italic>\n              included a 264-bp CDMS with 10 significant DMSs. Both regions also exhibited consistent methylation patterns in coronary tissues, comparing human coronary plaque to normal coronary artery samples. Additionally, the\n              <jats:italic toggle=\"yes\">HIPK3<\/jats:italic>\n              gene, which modulates STAT3 (signal transducer and activator of transcription 3) expression, thereby promoting osteoblast-like transformation in vascular smooth muscle cells, showed a CDMS with 5 significant DMSs within a 123-bp region, with further validation in the corresponding tissues. Furthermore, over 66% biomarkers demonstrated significant associations with mortality in patients with early-onset AMI, providing evidence of the impact of these biomarkers on the pathophysiology of the disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>This innovative epigenomic study into early-onset AMI not only identifies biomarkers associated with the disease and its mortality but also highlights the critical role of vascular smooth muscle cell phenotype regulation in early-onset AMI pathogenesis. Our findings suggest that changes in vascular smooth muscle cell phenotypes toward synthetic and osteoblast-like states play a crucial role in early-onset AMI.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.125.322503","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T09:00:18Z","timestamp":1744880418000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Epigenetic Modulation of Vascular Smooth Muscle Cell Phenotype Switching in Early-Onset Acute Myocardial Infarction"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4560-4142","authenticated-orcid":true,"given":"Yeonsu","family":"Jeon","sequence":"first","affiliation":[{"name":"Clinomics Inc., Osong, Republic of Korea (Y.J., Y.J.K., S.J., H.R., B.-C.K., Y. Kang, J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-2734","authenticated-orcid":true,"given":"Yoonsung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea (Y. Kwon, K.A., J.B.)"},{"name":"Department of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea (Y. Kwon, K.A., J.B.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9122-914X","authenticated-orcid":true,"given":"Yeo Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Clinomics Inc., Osong, Republic of Korea (Y.J., Y.J.K., S.J., H.R., B.-C.K., Y. Kang, J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwon","family":"Jeon","sequence":"additional","affiliation":[{"name":"Clinomics Inc., Osong, Republic of Korea (Y.J., Y.J.K., S.J., H.R., B.-C.K., Y. Kang, J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyojung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Clinomics Inc., Osong, Republic of Korea (Y.J., Y.J.K., S.J., H.R., B.-C.K., Y. Kang, J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungwhan","family":"An","sequence":"additional","affiliation":[{"name":"Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea (Y. Kwon, K.A., J.B.)"},{"name":"Department of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea (Y. Kwon, K.A., J.B.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7761-3217","authenticated-orcid":true,"given":"Byoung-Chul","family":"Kim","sequence":"additional","affiliation":[{"name":"Clinomics Inc., Osong, Republic of Korea (Y.J., Y.J.K., S.J., H.R., B.-C.K., Y. Kang, J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1264-9870","authenticated-orcid":true,"given":"Weon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea (W.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1386-349X","authenticated-orcid":true,"given":"Sang Yeub","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chung-Ang University College of Medicine, Chung-Ang University Gwangmyeong Hospital, Republic of Korea (S.Y.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1362-9804","authenticated-orcid":true,"given":"Jang-Whan","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea (J.-W.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6632-7239","authenticated-orcid":true,"given":"Jin-Yong","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea (J.-Y.H., M.G.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9672-1798","authenticated-orcid":true,"given":"Min Gyu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea (J.-Y.H., M.G.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-0851","authenticated-orcid":true,"given":"Younghui","family":"Kang","sequence":"additional","affiliation":[{"name":"Clinomics Inc., Osong, Republic of Korea (Y.J., Y.J.K., S.J., H.R., B.-C.K., Y. 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