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

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 Yeter, Natalia Solowjowa, Gabriela Salinas, Georg N. Duda, Volkmar Falk, Naren R. Vyavahare, Wolfgang M. Kuebler () and Christoph Knosalla ()
Additional contact information
Mariya M. Kucherenko: Deutsches Herzzentrum der Charité (DHZC)
Pengchao Sang: Deutsches Herzzentrum der Charité (DHZC)
Juquan Yao: Deutsches Herzzentrum der Charité (DHZC)
Tara Gransar: Deutsches Herzzentrum der Charité (DHZC)
Saphala Dhital: Clemson University
Jana Grune: Deutsches Herzzentrum der Charité (DHZC)
Szandor Simmons: Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Laura Michalick: Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
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)
Ruhi Yeter: Deutsches Herzzentrum der Charité (DHZC)
Natalia Solowjowa: Deutsches Herzzentrum der Charité (DHZC)
Gabriela Salinas: NGS Integrative Genomics (NIG)
Georg N. Duda: Berlin Institute of Health at Charité - Universitätsmedizin Berlin
Volkmar Falk: Deutsches Herzzentrum der Charité (DHZC)
Naren R. Vyavahare: Clemson University
Wolfgang M. Kuebler: Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Christoph Knosalla: Deutsches Herzzentrum der Charité (DHZC)

Nature Communications, 2023, vol. 14, issue 1, 1-23

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39934-z

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