{
    "abstract": "Small molecule inhibition of with no lysine kinase 1 (WNK1) (WNK463) signaling activates adenosine monophosphate-activated protein kinase signaling and mitigates membrane enrichment of glucose transporters 1 and 4, which decreases protein O-GlcNAcylation and glycation. Quantitative proteomics of right ventricular (RV) mitochondrial enrichments shows WNK463 prevents down-regulation of several mitochondrial metabolic enzymes. and metabolomics analysis suggests multiple metabolic processes are corrected. Physiologically, WNK463 augments RV systolic and diastolic function independent of pulmonary arterial hypertension severity. Hypochloremia, a condition of predicted WNK1 activation in patients with pulmonary arterial hypertension, is associated with more severe RV dysfunction. These results suggest WNK1 may be a druggable target to combat\u00a0metabolic dysregulation and may improve RV function and survival in pulmonary arterial hypertension.",
    "authors": [
        {
            "affiliation": "Lillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.",
            "firstname": "Sasha Z",
            "initials": "SZ",
            "lastname": "Prisco"
        },
        {
            "affiliation": "Lillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.",
            "firstname": "Megan",
            "initials": "M",
            "lastname": "Eklund"
        },
        {
            "affiliation": "Lillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.",
            "firstname": "Rashmi",
            "initials": "R",
            "lastname": "Raveendran"
        },
        {
            "affiliation": "Lillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.",
            "firstname": "Thenappan",
            "initials": "T",
            "lastname": "Thenappan"
        },
        {
            "affiliation": "Lillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.",
            "firstname": "Kurt W",
            "initials": "KW",
            "lastname": "Prins"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2021 The Authors.",
    "doi": "10.1016/j.jacbts.2021.09.004\n10.1101/2020.06.08.133769",
    "journal": "JACC. Basic to translational science",
    "keywords": [
        "AMPK, adenosine monophosphate-activated protein kinase",
        "AS160, 160\u00a0kDa substrate of the Akt serine/threonine kinase",
        "DCA, dicarboxylic fatty acid",
        "FAO, fatty acid oxidation",
        "GLO1, glyoxalase 1",
        "GLO2, glyoxalase 2",
        "GLUT1, glucose transporter 1",
        "GLUT4, glucose transporter 4",
        "LV, left ventricle/ventricular",
        "MCT, monocrotaline",
        "MCT-V, monocrotaline-vehicle",
        "PAH, pulmonary arterial hypertension",
        "PTM, post-translationally modify/modifications",
        "PV, pressure-volume",
        "PVR, pulmonary vascular resistance",
        "RA, right atrial",
        "RV, right ventricle/ventricular",
        "RVD, right ventricular dysfunction",
        "TCA, tricarboxylic acid",
        "Tau/\u03c4, right ventricular relaxation time",
        "UDP-GlcNAC, uridine diphosphate N-acetylglucosamine",
        "WNK, with no lysine kinase",
        "lipotoxicity",
        "metabolism",
        "mitochondria",
        "pulmonary arterial hypertension",
        "right ventricular dysfunction",
        "with no lysine kinase 1"
    ],
    "methods": null,
    "publication_date": "2021-12-07",
    "pubmed_id": "34869947\n29540357\n33426379\n30545976\n29263174\n30109950\n29695452\n22246173\n26060207\n24662662\n20651294\n31539311\n32067589\n23530187\n29698719\n32079477\n24803536\n28178566\n20937822\n30410865\n27911840\n29107506\n28974774\n16263722\n18270262\n27595330\n28566298\n23181072\n27006481\n24274756\n23152488\n20581101\n28081831\n27213235\n25918408\n26446791\n30586718\n33593071\n25416785\n26248993\n29893446\n29943886\n32971526\n21126971\n28624389\n32079620\n23794090\n25608554\n16051889\n32059997\n25287062\n20813867\n23111998\n25613900\n22887999",
    "results": null,
    "title": "With No Lysine Kinase 1 Promotes Metabolic Derangements and RV Dysfunction in Pulmonary Arterial\u00a0Hypertension.",
    "xml": "<Element 'PubmedArticle' at 0x788504ac92b0>"
}