Intermittent Hypoxia Mimicking Sleep Apnea Increases Passive Stiffness of Myocardial Extracellular Matrix. A Multiscale Study
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 stiffn...Continue Reading
References
Heterogeneous micromechanical properties of the extracellular matrix in healthy and infarcted hearts
Citations
Obstructive sleep apnoea, intermittent hypoxia and heart failure with a preserved ejection fraction.
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