Intermittent hypoxia mimicking sleep apnea increases passive stiffness of myocardial extracellular matrix. A multiscale study.
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- dc.contributor.author Farré López, Núria
- dc.contributor.author Otero, Jorge
- dc.contributor.author Falcones, Bryan
- dc.contributor.author Torres, Marta
- dc.contributor.author Jorba, Ignasi
- dc.contributor.author Gozal, David
- dc.contributor.author Almendros, Isaac
- dc.contributor.author Farré, Ramon
- dc.contributor.author Navajas, Daniel
- dc.date.accessioned 2019-04-30T07:49:40Z
- dc.date.available 2019-04-30T07:49:40Z
- dc.date.issued 2018
- dc.description.abstract 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% O2 40 s-6% O2 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 (EM) 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 (Em) 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 EM (p < 0.001) of young mice as compared with normoxic controls. In contrast, no significant differences emerged in Em 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.
- dc.description.sponsorship This work was supported in part by the Spanish Ministry of Economy and Competitiveness (FIS-PI14/00280, SAF2017-85574-R, and DPI2017-83721-P). DG was supported by the Herbert T. Abelson Chair in Pediatrics and by National Institutes of Health grant HL130984.
- dc.format.mimetype application/pdf
- dc.identifier.citation Farré N, Otero J, Falcones B, Torres M, Jorba I, Gozal D. et al. Intermittent hypoxia mimicking sleep apnea increases passive stiffness of myocardial extracellular matrix. A multiscale study. Front Physiol. 2018 Aug 15;9:1143. DOI: 10.3389/fphys.2018.01143
- dc.identifier.doi http://dx.doi.org/10.3389/fphys.2018.01143
- dc.identifier.issn 1664-042X
- dc.identifier.uri http://hdl.handle.net/10230/37156
- dc.language.iso eng
- dc.publisher Frontiers
- dc.relation.ispartof Frontiers in Physiology. 2018 Aug 15;9:1143
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-85574-R
- dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Atomic force microscopy
- dc.subject.keyword Heart mechanics
- dc.subject.keyword Myocardial stiffness
- dc.subject.keyword Obstructive sleep apnea
- dc.subject.keyword Tensile test
- dc.subject.keyword Ventricular strain
- dc.subject.other Apnea
- dc.subject.other Anoxèmia
- dc.subject.other Cor -- Malalties
- dc.title Intermittent hypoxia mimicking sleep apnea increases passive stiffness of myocardial extracellular matrix. A multiscale study.
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion