The mechanobiology of pulmonary vascular remodeling in the congenital absence of eNOS

Biomechanics and Modeling in Mechanobiology
Ryan W Kobs, Naomi C Chesler

Abstract

Primary pulmonary hypertension is a rare but deadly disease. Lungs extracted from PPH patients are deficient in endothelial nitric oxide synthase (eNOS), making the eNOS-null mouse a potentially useful model of the disease. To better understand the progression of pulmonary vascular remodeling in the congenital absence of eNOS, we induced pulmonary hypertension in eNOS-null mice using hypobaric hypoxia, and then quantified large artery structure and function in contralateral vessels. In particular, to assess structure we quantified diameter, wall thickness, and collagen, elastin and smooth muscle cell content; to quantify function we performed pressure-diameter tests. After remodeling, the pulmonary arteries had increased wall, collagen and elastin thicknesses compared to controls (P<0.05). The remodeled pulmonary arteries also had increased elastic moduli at low and high strains compared to controls (P<0.05). The increases in moduli at low and high strain correlated with increases in elastin and collagen thickness, respectively (P<0.05). These results provide insight into the mechanobiology of pulmonary vascular remodeling in the congenital absence of eNOS, and the coupled nature of these changes.

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Citations

May 4, 2011·Biomechanics and Modeling in Mechanobiology·Zhijie Wang, Naomi C Chesler
Dec 16, 2011·Medical & Biological Engineering & Computing·Gil MaromMoshe Rosenfeld
Jan 5, 2012·Cardiovascular Research·Philip M BauerJeffrey S Isenberg
Jul 29, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Steven R LammersRobin Shandas
Sep 21, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Chen Yen OoiNaomi C Chesler
Jun 28, 2011·The Journal of Sexual Medicine·Zili ZuoYong Cheng
Jul 21, 2007·The American Journal of Pathology·Steve D SwainAllen G Harmsen
Dec 21, 2011·Journal of Biomechanics·Diana M TabimaNaomi C Chesler
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Nov 20, 2014·Annals of the American Thoracic Society·Timothy E RaymondAdriano R Tonelli
Nov 25, 2016·American Journal of Physiology. Heart and Circulatory Physiology·R Blair DodsonErin K Zinkhan
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Aug 2, 2017·International Journal of Molecular Sciences·Christian JungMarcus Franz
Aug 21, 2018·Cellular and Molecular Bioengineering·Mark J GolobNaomi C Chesler
Apr 20, 2019·Frontiers in Physiology·Omid ForouzanNaomi C Chesler
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Nov 29, 2020·Free Radical Biology & Medicine·Tiago J CostaFrancesc Jiménez-Altayó
Apr 10, 2021·Journal of the Mechanical Behavior of Biomedical Materials·Reza PourmodhejiLik-Chuan Lee

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