{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:34:03Z","timestamp":1790879643228,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NMRPD1K0941, NZRPD1K0011"],"award-info":[{"award-number":["NMRPD1K0941, NZRPD1K0011"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3F2061, CMRPG3G1391, CORPG3J0291-3, CMRPG3G1371-3, CMRPD1J0082"],"award-info":[{"award-number":["CMRPG3F2061, CMRPG3G1391, CORPG3J0291-3, CMRPG3G1371-3, CMRPD1J0082"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with primary mitral regurgitation (MR) may remain asymptomatic for many years. For unknown reasons, some shift from a compensated to a decompensated state and progress to fatal heart failure. To elucidate the genetic determinants of this process, we recruited 28 patients who underwent mitral valve surgery and stratified them into control, compensated MR, and decompensated MR groups. Tissue biopsies were obtained from the patients\u2019 left ventricular (LV) lateral wall for a transcriptome-wide profiling of 64,769 probes to identify differentially expressed genes (DEGs). Using cutoff values at the 1% FDR significance level and sex- and age-adjusted regression models, we identified 12 significant DEGs (CTGF, MAP1B, SERPINE1, MYH9, MICAL2, MYO1D, CRY1, AQP7P3, HTRA1, PRSS23, IGFBP2, and FN1). The most significant gene was CTGF (adjusted R2 = 0.74, p = 1.80 \u00d7 10\u22128). We found that the majority of genes expressed in the more advanced decompensated MR group were pro-fibrotic genes associated with cardiac fibrosis. In particular, six pro-fibrotic genes (CTGF, SERPINE1, MYH9, HTRA1, PRSS23, and FN1) were overexpressed and enriched in pathways involved in ECM (extracellular matrix) protein remodeling. Therapeutic interventions that antagonize these six genes may slow the progression toward decompensated MR.<\/jats:p>","DOI":"10.3390\/ijms22073454","type":"journal-article","created":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T22:09:01Z","timestamp":1616969341000},"page":"3454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Gene Expression Changes of Humans with Primary Mitral Regurgitation and Reduced Left Ventricular Ejection Fraction"],"prefix":"10.3390","volume":"22","author":[{"given":"Feng-Chun","family":"Tsai","sequence":"first","affiliation":[{"name":"Division of Cardiac Surgery, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan"},{"name":"School of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chang Gung University, Taoyuan City 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Chi","family":"Yen","sequence":"additional","affiliation":[{"name":"School of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan"},{"name":"Cardiovascular Department, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsun","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan"},{"name":"Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Hsuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chang Gung University, Taoyuan City 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Hsin","family":"Yeh","sequence":"additional","affiliation":[{"name":"School of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan"},{"name":"Cardiovascular Department, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Chien","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chang Gung University, Taoyuan City 33302, Taiwan"},{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan City 33302, Taiwan"},{"name":"Healthy Aging Research Center, Chang Gung University, Taoyuan City 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.jcmg.2018.01.009","article-title":"Mitral Valve Regurgitation in the Contemporary Era: Insights Into Diagnosis, Management, and Future Directions","volume":"11","author":"Reddy","year":"2018","journal-title":"JACC Cardiovasc. 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