{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:13:53Z","timestamp":1792030433791,"version":"4.4.0"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)\/National Heart, Lung, and Blood Institute (NHLBI)","award":["K08HL131987"],"award-info":[{"award-number":["K08HL131987"]}]},{"name":"National Institutes of Health (NIH)\/National Heart, Lung, and Blood Institute (NHLBI)","award":["R01HL152090"],"award-info":[{"award-number":["R01HL152090"]}]},{"name":"National Institutes of Health (NIH)\/National Heart, Lung, and Blood Institute (NHLBI)","award":["R21HL154028"],"award-info":[{"award-number":["R21HL154028"]}]},{"name":"National Institutes of Health (NIH)\/National Heart, Lung, and Blood Institute (NHLBI)","award":["R01HL150266"],"award-info":[{"award-number":["R01HL150266"]}]},{"name":"NIH\/NHLBI Research Grants","award":["K08HL131987"],"award-info":[{"award-number":["K08HL131987"]}]},{"name":"NIH\/NHLBI Research Grants","award":["R01HL152090"],"award-info":[{"award-number":["R01HL152090"]}]},{"name":"NIH\/NHLBI Research Grants","award":["R21HL154028"],"award-info":[{"award-number":["R21HL154028"]}]},{"name":"NIH\/NHLBI Research Grants","award":["R01HL150266"],"award-info":[{"award-number":["R01HL150266"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Myocardial fibrosis is a common postmortem finding among individuals with Sudden Cardiac Death (SCD). Numerous in vivo and in vitro studies have shown that increased galectin-3 (gal3) expression into the myocardium is associated with higher incidence of fibrosis. Although elevated gal3 expression is linked with myocardial fibrosis, its role in predicting the risk of SCD is unknown. Methods: We reviewed the clinical datasets and post-mortem examination of 221 subjects who had died suddenly. We examined myocardial pathology including the extent of cardiac hypertrophy, fibrosis, and the degree of coronary atherosclerosis in these subjects. In a select group of SCD subjects, we studied myocardial gal3 and periostin expression using immunohistochemistry. To further examine if a higher level of circulating gal3 can be detected preceding sudden death, we measured serum gal3 in a porcine model of subtotal coronary artery ligation which shows an increased tendency to develop lethal cardiac arrhythmias, including ventricular tachycardia or fibrillation. Results: Of the total 1314 human subjects screened, 12.7% had SCD. Comparison of age-matched SCD with non-SCD subjects showed that SCD groups had excessive myocardial fibrosis involving both the left ventricular free wall and interventricular septum. In pigs with subtotal coronary artery ligation and SCD, we detected significantly elevated circulating gal3 levels approximately 10 days preceding the SCD event. Immunohistochemistry showed increased myocardial gal3 and periostin expression in pigs that died suddenly, compared to the controls. Conclusion: Our study shows that increased gal3 is associated with a higher risk of myocardial fibrosis and the risk of SCD. This supports the importance of larger translational studies to target gal3 to prevent cardiac fibrosis and attenuate the risk of SCD.<\/jats:p>","DOI":"10.3390\/cells12091218","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T01:35:44Z","timestamp":1682300144000},"page":"1218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Galectin-3 Is Associated with Cardiac Fibrosis and an Increased Risk of Sudden Death"],"prefix":"10.3390","volume":"12","author":[{"given":"Mingma D.","family":"Sherpa","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Jacob\u2019s School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati D.","family":"Sonkawade","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Jacob\u2019s School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinesh","family":"Jonnala","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Jacob\u2019s School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saraswati","family":"Pokharel","sequence":"additional","affiliation":[{"name":"Division of Thoracic Pathology and Oncology, Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8645-4203","authenticated-orcid":false,"given":"Mahyar","family":"Khazaeli","sequence":"additional","affiliation":[{"name":"Department of Pathology, Jacob\u2019s School of Medicine and Biomedical Sciences, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yatsynovich","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Jacob\u2019s School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-4561","authenticated-orcid":false,"given":"Mohamad A.","family":"Kalot","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Jacob\u2019s School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Weil","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Jacob\u2019s School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"John M.","family":"Canty","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Jacob\u2019s School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0476-2523","authenticated-orcid":false,"given":"Umesh C.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Jacob\u2019s School of Medicine and Biomedical Sciences, University at Buffalo, 875 Ellicott Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1161\/CIRCULATIONAHA.111.023846","article-title":"Sudden cardiac death caused by coronary heart disease","volume":"125","author":"Myerburg","year":"2012","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e001195","DOI":"10.1136\/openhrt-2019-001195","article-title":"Cardiac arrest and sudden cardiac death registries: A systematic review of global coverage","volume":"7","author":"Paratz","year":"2020","journal-title":"Open Heart"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e654","DOI":"10.1161\/CIR.0000000000000747","article-title":"Sudden Cardiac Arrest Survivorship: A Scientific Statement From the American Heart 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