Web of Science: 23 cites, Scopus: 29 cites, Google Scholar: cites,
Intermittent Hypoxia Mimicking Sleep Apnea Increases Passive Stiffness of Myocardial Extracellular Matrix. A Multiscale Study
Farré, Núria (Universitat Autònoma de Barcelona. Departament de Medicina)
Otero, Jorge (Universitat de Barcelona)
Falcones, Bryan (Universitat de Barcelona)
Torres, Marta (Hospital Clínic i Provincial de Barcelona)
Jorba, Ignasi (Universitat de Barcelona)
Gozal, David (University of Missouri School of Medicine)
Almendros, Isaac (Universitat de Barcelona)
Farré, Ramon (Universitat de Barcelona)
Navajas, Daniel (Universitat de Barcelona)

Data: 2018
Resum: Background: Tissue hypoxia-reoxygenation characterizes obstructive sleep apnea (OSA), a very prevalent respiratory disease associated with increased cardiovascular morbidity and mortality. Experimental studies indicate that intermittent hypoxia (IH) mimicking OSA induces oxidative stress and inflammation in heart tissue at the cell and molecular levels. However, it remains unclear whether IH modifies the passive stiffness of the cardiac tissue extracellular matrix (ECM). Aim: To investigate multiscale changes of stiffness induced by chronic IH in the ECM of left ventricular (LV) myocardium in a murine model of OSA. Methods: Two-month and 18-month old mice (N = 10 each) were subjected to IH (20% O 40 s-6% O 20 s) for 6 weeks (6 h/day). Corresponding control groups for each age were kept under normoxia. Fresh LV myocardial strips (∼7 mm × 1 mm × 1 mm) were prepared, and their ECM was obtained by decellularization. Myocardium ECM macroscale mechanics were measured by performing uniaxial stress-strain tensile tests. Strip macroscale stiffness was assessed as the stress value (σ) measured at 0. 2 strain and Young's modulus (E ) computed at 0. 2 strain by fitting Fung's constitutive model to the stress-strain relationship. ECM stiffness was characterized at the microscale as the Young's modulus (E ) measured in decellularized tissue slices (∼12 μm tick) by atomic force microscopy. Results: Intermittent hypoxia induced a ∼1. 5-fold increase in σ (p < 0. 001) and a ∼2. 5-fold increase in E (p < 0. 001) of young mice as compared with normoxic controls. In contrast, no significant differences emerged in E among IH-exposed and normoxic mice. Moreover, the mechanical effects of IH on myocardial ECM were similar in young and aged mice. Conclusion: The marked IH-induced increases in macroscale stiffness of LV myocardium ECM suggests that the ECM plays a role in the cardiac dysfunction induced by OSA. Furthermore, absence of any significant effects of IH on the microscale ECM stiffness suggests that the significant increases in macroscale stiffening are primarily mediated by 3D structural ECM remodeling.
Ajuts: Ministerio de Economía y Competitividad FIS-PI14/00280
Agencia Estatal de Investigación SAF2017-85574-R
Agencia Estatal de Investigación DPI2017-83721-P
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Atomic force microscopy ; Tensile test ; Heart mechanics ; Myocardial stiffness ; Ventricular strain ; Obstructive sleep apnea
Publicat a: Frontiers in physiology, Vol. 9 (august 2018) , ISSN 1664-042X

DOI: 10.3389/fphys.2018.01143
PMID: 30158879


10 p, 871.3 KB

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