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

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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 14 Issue 1 Pg. 4416 (07 21 2023) ISSN: 2041-1723 [Electronic] England
• PMID: 37479718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Elastin

Topics

• Humans
• Animals
• Rats
• Hypertension, Pulmonary
• Pulmonary Artery
• Biomechanical Phenomena
• Elastin
• Heart Diseases