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, Christoph Knosalla
Deutsches Herzzentrum der Charité. Charité-Universitätsmedizin Berlin. Freie Universität Berlin and Humboldt-Universität zu Berlin. Clemson University. NGS Integrative Genomics. Translational Cardiovascular Technology. University of Toronto.
Germany, United States, Switzerland and Canada
Nature Communications
Nat Commun 2023; 14
DOI: 10.1038/s41467-023-39934-z
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.
Category
Class II. Pulmonary Hypertension Associated with Left Ventricular Systolic or Diastolic Dysfunction
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes