{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T01:53:53Z","timestamp":1773885233153,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T00:00:00Z","timestamp":1595030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The molecular mechanism for worsening left ventricular (LV) function after mitral valve (MV) repair for chronic mitral regurgitation remains unknown. We wished to assess the LV transcriptome and identify determinants associated with worsening LV function post-MV repair. A total of 13 patients who underwent MV repair for chronic primary mitral regurgitation were divided into two groups, preserved LV function (N = 8) and worsening LV function (N = 5), for the study. Specimens of LV from the patients taken during surgery were used for the gene microarray study. Cardiomyocyte cell line HL-1 cells were transfected with gene-containing plasmids and further evaluated for mRNA and protein expression, apoptosis, and contractile protein degradation. Of 67,258 expressed sequence tags, microarrays identified 718 genes to be differentially expressed between preserved-LVF and worsening-LVF, including genes related to the protein ubiquitination pathway, bone morphogenetic protein (BMP) receptors, and regulation of eIF4 and p70S6K signaling. In addition, worsening-LVF was associated with altered expressions of genes pathologically relevant to heart failure, such asdownregulated apelin receptors and upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). HL-1 cardiomyocyte cells transfected with ubiquitination-related genes demonstrated activation of the protein ubiquitination pathwaywith an increase in the ubiquitin activating enzyme E1 (UAE-E1). It also led to increased apoptosis, downregulated and ubiquitinated X-linked inhibitor of apoptosis protein (XIAP), and reduced cell viability. Overexpression of ubiquitination-related genes also resulted in degradation and increased ubiquitination of \u03b1-smooth muscle actin (SMA). In conclusion, worsening-LVF presented differential gene expression profiles from preserved-LVF after MV repair. Upregulation of protein ubiquitination-related genes associated with worsening-LVF after MV repair may exert adverse effects on LV through increased apoptosis and contractile protein degradation.<\/jats:p>","DOI":"10.3390\/ijms21145073","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T06:08:17Z","timestamp":1595225297000},"page":"5073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ubiquitin Pathway Is Associated with Worsening Left Ventricle Function after Mitral Valve Repair: A Global Gene Expression Study"],"prefix":"10.3390","volume":"21","author":[{"given":"Feng-Chun","family":"Tsai","sequence":"first","affiliation":[{"name":"Division of Cardiovascular and Thoracic Surgery, Chang-Gung Memorial Hospital, Taoyuan 333, Taiwan"},{"name":"College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-8758","authenticated-orcid":false,"given":"Gwo-Jyh","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9750-7649","authenticated-orcid":false,"given":"Ying-Ju","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Respiratory Therapy, Chang-Gung University College of Medicine, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang-Hung","family":"Chang","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan"},{"name":"Cardiovascular Department, Chang-Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Jan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan"},{"name":"Cardiovascular Department, Chang-Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Hsin","family":"Yeh","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan"},{"name":"Cardiovascular Department, Chang-Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jtcvs.2014.05.014","article-title":"2014 AHA\/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"148","author":"Nishimura","year":"2014","journal-title":"J. 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