PEER-REVIEWED PUBLICATION

2025

Right Ventricular Stiffening and Function Are Associated With Main Pulmonary Artery Remodeling in a Rat Model of Pulmonary Hypertension

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Mirani B, Dauz JD, et al.

Arteriosclerosis, Thrombosis, and Vascular Biology

University of Toronto, Hospital for Sick Children, Ted Rogers Center for Heart Research, Harvard Medical School, Brigham and Women's Hospital, University of South Florida

RESEARCH SUMMARY
This study investigated how pulmonary arterial stiffening contributes to right ventricular (RV) remodeling, mechanics, and dysfunction in a sugen-hypoxia rat model of pulmonary arterial hypertension (PAH). The main pulmonary artery (mPA) and RV free wall were examined for structure, composition, and passive mechanical properties using biaxial testing, histology, and biochemical assays. The results demonstrated marked increases in collagen deposition, glycosaminoglycan content, and collagen-to-elastin ratios in both mPA and RV tissues, leading to anisotropic stiffening—particularly in the longitudinal direction. The degree of mPA stiffening correlated strongly with RV wall stiffness, active tension, and reduced RV-PA coupling efficiency, suggesting that proximal artery compliance plays a central role in right heart failure progression.
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CELLSCALE INSTRUMENT USED

BioTester

Biaxial tensile tests were conducted on rat main pulmonary artery and right ventricular free-wall tissues using a CellScale BioTester 5000. Samples were subjected to controlled equibiaxial loading cycles under defined longitudinal and circumferential stretch ratios. Membrane tension–strain data were analyzed with a 7-parameter Fung model to quantify low- and high-strain stiffness, anisotropy, and mechanical coupling between PA and RV tissues. The BioTester enabled precise measurement of passive viscoelastic behavior, revealing disease-related anisotropic stiffening patterns consistent with PAH remodeling.
AUTHORS

Bahram Mirani, John D. Dauz, Kana Yazaki, Neda Latifi, J. Paul Santerre, Michelle P. Bendeck, Craig A. Simmons, Mark K. Friedberg.

PUBLICATION DETAILS
JOURNAL

Arteriosclerosis, Thrombosis, and Vascular Biology

YEAR

2025

INSTITUTIONS

University of Toronto, Hospital for Sick Children, Ted Rogers Center for Heart Research, Harvard Medical School, Brigham and Women's Hospital, University of South Florida

COUNTRIES

Canada, United States

INSTRUMENT USED

BioTester

TESTING METHODS

Biaxial TestingTensile Testing

RESEARCH APPLICATIONS

Cardiac Tissue Engineering & MechanicsFibrosis & Tissue RemodelingMechanotransductionVascular Tissue Engineering & Mechanics

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