{
    "abstract": "We investigated the extent, biologic characterization, phenotypic specificity, and possible regulation of a \u03b21-adrenergic receptor-linked (\u03b21-AR-linked) gene signaling network (\u03b21-GSN) involved in left ventricular (LV) eccentric pathologic remodeling. A 430-member \u03b21-GSN was identified by mRNA expression in transgenic mice overexpressing human \u03b21-ARs or from literature curation, which exhibited opposite directional behavior in interventricular septum endomyocardial biopsies taken from patients with beta-blocker-treated, reverse remodeled dilated cardiomyopathies. With reverse remodeling, the major biologic categories and percentage of the dominant directional change were as follows: metabolic (19.3%, 81% upregulated); gene regulation (14.9%, 78% upregulated); extracellular matrix/fibrosis (9.1%, 92% downregulated); and cell homeostasis (13.3%, 60% upregulated). Regarding the comparison of \u03b21-GSN categories with expression from 19,243 nonnetwork genes, phenotypic selection for major \u03b21-GSN categories was exhibited for LV end systolic volume (contractility measure), ejection fraction (remodeling index), and pulmonary wedge pressure (wall tension surrogate), beginning at 3 months and persisting to study completion at 12 months. In addition, 121 lncRNAs were identified as possibly involved in cis-acting regulation of \u03b21-GSN members. We conclude that an extensive 430-member gene network downstream from the \u03b21-AR is involved in pathologic ventricular remodeling, with metabolic genes as the most prevalent category.",
    "authors": [
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.",
            "firstname": "Philip D",
            "initials": "PD",
            "lastname": "Tatman"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.\nColorado Center for Personalized Medicine University of Colorado School of Medicine, Aurora, Colorado, USA.",
            "firstname": "David P",
            "initials": "DP",
            "lastname": "Kao"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.\nDepartment of Pediatric Cardiology, Children's Hospital Colorado, Aurora, Colorado, USA.",
            "firstname": "Kathryn C",
            "initials": "KC",
            "lastname": "Chatfield"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.\nARCA biopharma, Westminster, Colorado, USA.",
            "firstname": "Ian A",
            "initials": "IA",
            "lastname": "Carroll"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.",
            "firstname": "Jessica A",
            "initials": "JA",
            "lastname": "Wagner"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.",
            "firstname": "Eric R",
            "initials": "ER",
            "lastname": "Jonas"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.",
            "firstname": "Carmen C",
            "initials": "CC",
            "lastname": "Sucharov"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.",
            "firstname": "J David",
            "initials": "JD",
            "lastname": "Port"
        },
        {
            "affiliation": "Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.",
            "firstname": "Brian D",
            "initials": "BD",
            "lastname": "Lowes"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.",
            "firstname": "Wayne A",
            "initials": "WA",
            "lastname": "Minobe"
        },
        {
            "affiliation": "ARCA biopharma, Westminster, Colorado, USA.",
            "firstname": "Sophia P",
            "initials": "SP",
            "lastname": "Huebler"
        },
        {
            "affiliation": "Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, Colorado, USA.",
            "firstname": "Anis",
            "initials": "A",
            "lastname": "Karimpour-Fard"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.",
            "firstname": "Erin M",
            "initials": "EM",
            "lastname": "Rodriguez"
        },
        {
            "affiliation": "Departments of Medicine and Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.",
            "firstname": "Stephen B",
            "initials": "SB",
            "lastname": "Liggett"
        },
        {
            "affiliation": "Division of Cardiology, Department of Medicine, and.\nARCA biopharma, Westminster, Colorado, USA.",
            "firstname": "Michael R",
            "initials": "MR",
            "lastname": "Bristow"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.1172/jci.insight.169720\n10.1161/CIRCRESAHA.111.245092\n10.1016/j.jchf.2017.09.009\n10.1161/CIRCGENETICS.114.000767\n10.1152/physiolgenomics.90225.2008\n10.1152/physiolgenomics.00067.2011\n10.1152/ajpheart.00017.2006\n10.1152/ajpheart.1995.269.2.H638\n10.1016/j.jacbts.2016.02.001\n10.1371/journal.pone.0221519\n10.1073/pnas.241393598\n10.1016/j.tcm.2007.10.002\n10.1007/BF00794061\n10.1152/physiolgenomics.00122.2001\n10.1007/s00059-017-4564-3\n10.1161/CIRCULATIONAHA.119.042178\n10.1056/NEJMoa012630\n10.1096/fj.05-5414com\n10.1073/pnas.1600633113\n10.1007/s10974-010-9224-7\n10.3892/or.2015.3988\n10.1038/cdd.2015.143\n10.1152/ajpheart.00867.2011\n10.1016/j.bbalip.2016.03.015\n10.1007/s10930-017-9734-x\n10.1016/j.bbrc.2010.09.109\n10.1007/s11010-005-5535-1\n10.1093/eurjhf/hfr152\n10.1016/j.febslet.2005.11.046\n10.1172/JCI2950\n10.1016/j.mce.2009.05.006\n10.1210/me.14.7.986\n10.1016/j.yjmcc.2014.05.002\n10.1161/01.RES.0000014966.97486.C0\n10.1038/s41594-020-0446-0\n10.1038/nature07511\n10.1016/j.lfs.2017.10.034\n10.1161/01.CIR.94.11.2837\n10.1152/ajpcell.00167.2022\n10.1080/00031305.1998.10480551\n10.1161/01.CIR.56.5.845\n10.1172/jci.insight.89169\n10.1016/j.celrep.2016.06.074\n10.12688/f1000research.11339.1\n10.1016/j.bbagen.2013.10.035\n10.1038/s41580-020-00315-9\n10.1016/j.jacbts.2022.08.005\n10.1093/bioinformatics/btg167\n10.1037/a0028087\n10.1093/bioinformatics/btw313",
    "journal": "JCI insight",
    "keywords": [
        "Bioinformatics",
        "Cardiology",
        "Genetics",
        "Heart failure",
        "Molecular genetics"
    ],
    "methods": null,
    "publication_date": "2023-08-22",
    "pubmed_id": "37606047\n22034480\n29096787\n25637602\n18664629\n21954455\n16501029\n7653628\n30167508\n31469842\n11717446\n18206802\n9202848\n12118103\n28444413\n31801360\n11986409\n16675844\n27325775\n20706863\n25998939\n26517531\n22081703\n27004753\n28755312\n20888800\n16132722\n22143674\n16343488\n9616213\n19465082\n10894149\n24838003\n11964375\n32514177\n19043405\n29107793\n8941110\n35759434\n71960\n28138556\n27425608\n28721198\n24184936\n33353982\n36281440\n12874044\n22563845\n27207943",
    "results": null,
    "title": "An extensive \u03b21-adrenergic receptor gene signaling network regulates molecular remodeling in dilated cardiomyopathies.",
    "xml": "<Element 'PubmedArticle' at 0x78850434b560>"
}