Arterial Wall Stiffening in Caveolin-1 Deficiency-Induced Pulmonary Artery Hypertension in Mice
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SP ISS: EXPERIMENTAL ADVANCES IN CARDIOVASCULAR BIOMECHANICS
Arterial Wall Stiffening in Caveolin-1 Deficiency-Induced Pulmonary Artery Hypertension in Mice J. Moreno 1,2 & D. Escobedo 3 & C. Calhoun 3 & C. Jourdan Le Saux 3,4 & H. C. Han 1,2 Received: 3 January 2020 / Accepted: 8 September 2020 # Society for Experimental Mechanics 2020
Abstract Background Pulmonary artery hypertension (PAH) is a complex disorder that can lead to right heart failure. The generation of caveolin-1 deficient mice (CAV-1−/−) has provided an alternative genetic model to study the mechanisms of pulmonary hypertension. However, the vascular adaptations in these mice have not been characterized. Objective To determine the histological and functional changes in the pulmonary and carotid arteries in CAV-1−/− induced PAH. Methods Pulmonary and carotid arteries of young (4–6 months old) and mature (9–12 months old) CAV-1−/− mice were tested and compared to normal wild type mice. Results Artery stiffness increases in CAV-1−/− mice, especially the circumferential stiffness of the pulmonary arteries. Increases in stiffness were quantified by a decrease in circumferential stretch and transition strain, increases in elastic moduli, and an increase in total strain energy at physiologic strains. Changes in mechanical properties for the pulmonary artery correlated with increased collagen content while changes in the carotid artery correlated with decreased elastin content. Conclusions We demonstrated that an increase in artery stiffness is associated with CAV-1 deficiency-induced pulmonary hypertension. These results improve our understanding of arterial remodeling in PAH. Keywords Pulmonary hypertension . Mechanical stiffness . Arteries . Caveolin-1 deficiency . Mice
Introduction Pulmonary artery hypertension (PAH) is a complex disorder characterized by a sustained elevation in mean pulmonary artery pressure (MPAP > 25 mm Hg) due to increased pulmonary resistance, ultimately leading to right ventricle hypertrophy and failure [1, 2]. The hypertensive pressure in pulmonary arteries results in artery stiffening which contributes to an * C. Jourdan Le Saux [email protected] * H. C. Han [email protected] 1
Department of Mechanical Engineering, University of Texas at San Antonio, San Antonio, TX 78249, USA
2
Biomedical Engineering Program, UTSA-UTHSCSA, San Antonio, TX, USA
3
Department of Medicine/Cardiology, University of Texas Health Science Center At San Antonio, San Antonio, TX, USA
4
Department of Medicine/Pulmonary and Critical Care, University of California San Francisco, San Francisco, CA 94143, USA
increased ventricular after-load and right ventricular hypertrophy [3]. Pulmonary vascular remodeling in PAH is characterized by vessel wall thickening due to hypertrophy and/or hyperplasia of the vascular cells (fibroblasts and smooth muscle cells) and an increased extracellular matrix (ECM, collagen, elastin and fibronectin) [4–6]. Clinical studies have demonstrated that large pulmonary artery (PA) stiffening is a predictor of patient mo
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