Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension

Mark J Golob; Diana M Tabima; Gregory D Wolf; James L Johnston; Omid Forouzan; Ashley M Mulchrone; Heidi B Kellihan; Melissa L Bates; Naomi C Chesler

doi:10.1016/j.jbiomech.2017.02.003

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Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension

Journal article

Peer reviewed

Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension

Mark J Golob, Diana M Tabima, Gregory D Wolf, James L Johnston, Omid Forouzan, Ashley M Mulchrone, Heidi B Kellihan, Melissa L Bates and Naomi C Chesler

Journal of biomechanics, Vol.55, pp.92-98

04/11/2017

DOI: 10.1016/j.jbiomech.2017.02.003

PMCID: PMC5535793

PMID: 28262286

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http://doi.org/10.1016/j.jbiomech.2017.02.003View

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Abstract

Pulmonary hypertension (PH) is a debilitating vascular disease that leads to pulmonary artery (PA) stiffening, which is a predictor of patient mortality. During PH development, PA stiffening adversely affects right ventricular function. PA stiffening has been investigated through the arterial nonlinear elastic response during mechanical testing using a canine PH model. However, only circumferential properties were reported and in the absence of chronic PH-induced PA remodeling. Remodeling can alter arterial nonlinear elastic properties via chronic changes in extracellular matrix (ECM) content and geometry. Here, we used an established constitutive model to demonstrate and differentiate between strain-stiffening, which is due to nonlinear elasticity, and remodeling-induced stiffening, which is due to ECM and geometric changes, in a canine model of chronic thromboembolic PH (CTEPH). To do this, circumferential and axial tissue strips of large extralobar PAs from control and CTEPH tissues were tested in uniaxial tension, and data were fit to a phenomenological constitutive model. Strain-induced stiffening was evident from mechanical testing as nonlinear elasticity in both directions and computationally by a high correlation coefficient between the mechanical data and model (R =0.89). Remodeling-induced stiffening was evident from a significant increase in the constitutive model stress parameter, which correlated with increased PA collagen content and decreased PA elastin content as measured histologically. The ability to differentiate between strain- and remodeling-induced stiffening in vivo may lead to tailored clinical treatments for PA stiffening in PH patients.

Vascular Remodeling

Elasticity

Hypertension, Pulmonary - physiopathology

Stress, Mechanical

Male

Hypertension, Pulmonary - metabolism

Pulmonary Artery - physiopathology

Collagen - metabolism

Animals

Dogs

Extracellular Matrix - pathology

Hypertension, Pulmonary - pathology

Pulmonary Artery - pathology

Disease Models, Animal

Details

Title: Subtitle: Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension
Creators: Mark J Golob - Department of Biomedical Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI 53706, United States
Diana M Tabima - Department of Biomedical Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI 53706, United States
Gregory D Wolf - Department of Biomedical Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI 53706, United States
James L Johnston - Department of Biomedical Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI 53706, United States
Omid Forouzan - Department of Biomedical Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI 53706, United States
Ashley M Mulchrone - Department of Biomedical Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI 53706, United States
Heidi B Kellihan - Department of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, United States
Melissa L Bates - Department of Physiology, University of Iowa, Iowa City, IA 52242, United States
Naomi C Chesler - Department of Biomedical Engineering, University of Wisconsin-Madison College of Engineering, Madison, WI 53706, United States. Electronic address: Naomi.Chesler@wisc.edu
Resource Type: Journal article
Publication Details: Journal of biomechanics, Vol.55, pp.92-98
DOI: 10.1016/j.jbiomech.2017.02.003
PMID: 28262286
PMCID: PMC5535793
NLM abbreviation: J Biomech
ISSN: 0021-9290
eISSN: 1873-2380
Publisher: United States
Grant note: R01 HL105598 / NHLBI NIH HHS
Language: English
Date published: 04/11/2017
Academic Unit: Stead Family Department of Pediatrics; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984002357302771

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