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Elastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease

Author

Listed:
  • Mariya M. Kucherenko

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    DZHK (German Centre for Cardiovascular Research))

  • Pengchao Sang

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    DZHK (German Centre for Cardiovascular Research))

  • Juquan Yao

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Tara Gransar

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin)

  • Saphala Dhital

    (Clemson University)

  • Jana Grune

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    DZHK (German Centre for Cardiovascular Research))

  • Szandor Simmons

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    DZHK (German Centre for Cardiovascular Research))

  • Laura Michalick

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    DZHK (German Centre for Cardiovascular Research))

  • Dag Wulsten

    (Berlin Institute of Health at Charité - Universitätsmedizin Berlin)

  • Mario Thiele

    (Berlin Institute of Health at Charité - Universitätsmedizin Berlin)

  • Orr Shomroni

    (NGS Integrative Genomics (NIG))

  • Felix Hennig

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    DZHK (German Centre for Cardiovascular Research))

  • Ruhi Yeter

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany)

  • Natalia Solowjowa

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    DZHK (German Centre for Cardiovascular Research))

  • Gabriela Salinas

    (NGS Integrative Genomics (NIG))

  • Georg N. Duda

    (Berlin Institute of Health at Charité - Universitätsmedizin Berlin
    Berlin Institute of Health at Charité - Universitätsmedizin Berlin)

  • Volkmar Falk

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    DZHK (German Centre for Cardiovascular Research)
    Translational Cardiovascular Technology, LFW C 13.2, ETH Zurich)

  • Naren R. Vyavahare

    (Clemson University)

  • Wolfgang M. Kuebler

    (Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
    DZHK (German Centre for Cardiovascular Research)
    University of Toronto)

  • Christoph Knosalla

    (Deutsches Herzzentrum der Charité (DHZC)
    corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
    DZHK (German Centre for Cardiovascular Research))

Abstract

Pulmonary hypertension worsens outcome in left heart disease. Stiffening of the pulmonary artery may drive this pathology by increasing right ventricular dysfunction and lung vascular remodeling. Here we show increased stiffness of pulmonary arteries from patients with left heart disease that correlates with impaired pulmonary hemodynamics. Extracellular matrix remodeling in the pulmonary arterial wall, manifested by dysregulated genes implicated in elastin degradation, precedes the onset of pulmonary hypertension. The resulting degradation of elastic fibers is paralleled by an accumulation of fibrillar collagens. Pentagalloyl glucose preserves arterial elastic fibers from elastolysis, reduces inflammation and collagen accumulation, improves pulmonary artery biomechanics, and normalizes right ventricular and pulmonary hemodynamics in a rat model of pulmonary hypertension due to left heart disease. Thus, targeting extracellular matrix remodeling may present a therapeutic approach for pulmonary hypertension due to left heart disease.

Suggested Citation

  • Mariya M. Kucherenko & Pengchao Sang & Juquan Yao & Tara Gransar & Saphala Dhital & Jana Grune & Szandor Simmons & Laura Michalick & Dag Wulsten & Mario Thiele & Orr Shomroni & Felix Hennig & Ruhi Yet, 2023. "Elastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39934-z
    DOI: 10.1038/s41467-023-39934-z
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    References listed on IDEAS

    as
    1. A. Petersen & A. Princ & G. Korus & A. Ellinghaus & H. Leemhuis & A. Herrera & A. Klaumünzer & S. Schreivogel & A. Woloszyk & K. Schmidt-Bleek & S. Geissler & I. Heschel & G. N. Duda, 2018. "A biomaterial with a channel-like pore architecture induces endochondral healing of bone defects," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    2. Mariya M. Kucherenko & Halyna R. Shcherbata, 2018. "Stress-dependent miR-980 regulation of Rbfox1/A2bp1 promotes ribonucleoprotein granule formation and cell survival," Nature Communications, Nature, vol. 9(1), pages 1-20, December.
    Full references (including those not matched with items on IDEAS)

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