Kai Jiang1, Sen Jiao1, Megan Vitko2, Rebecca Darrah2, Chris A Flask3, Craig A Hodges4, Xin Yu5. 1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. 2. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA. 3. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Department of Radiology, Case Western Reserve University, Cleveland, OH, USA; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. 4. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA. 5. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Department of Radiology, Case Western Reserve University, Cleveland, OH, USA; Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: xin.yu@case.edu.
Abstract
BACKGROUND: Altered cardiac function has been observed in cystic fibrosis transmembrane regulator (CFTR) knockout mice. However, whether this alteration is a direct effect of CFTR disruption in the heart, or is secondary due to systemic loss of CFTR, remains to be elucidated. METHODS: Cardiac function of mice with muscle-specific or global knockout of CFTR was evaluated at baseline and under β-stimulation by MRI in vivo. Myocyte contractility and Ca2+ transients were measured in vitro. RESULTS: Both CFTR knockout models showed increased twist and torsion at baseline. Response to β-stimulation was unaltered in muscle-specific CFTR knockout mice and was slightly decreased in global CFTR knockout mice. Aortic diameter was also decreased in both mouse models. No difference was observed in myocyte contractility and Ca2+ transients. CONCLUSIONS: CFTR disruption leads to increased myocardial contractility at baseline, which may trigger untoward myocardial remodeling in CF patients that is independent of lung diseases.
BACKGROUND: Altered cardiac function has been observed in cystic fibrosis transmembrane regulator (CFTR) knockout mice. However, whether this alteration is a direct effect of CFTR disruption in the heart, or is secondary due to systemic loss of CFTR, remains to be elucidated. METHODS: Cardiac function of mice with muscle-specific or global knockout of CFTR was evaluated at baseline and under β-stimulation by MRI in vivo. Myocyte contractility and Ca2+ transients were measured in vitro. RESULTS: Both CFTR knockout models showed increased twist and torsion at baseline. Response to β-stimulation was unaltered in muscle-specific CFTR knockout mice and was slightly decreased in global CFTR knockout mice. Aortic diameter was also decreased in both mouse models. No difference was observed in myocyte contractility and Ca2+ transients. CONCLUSIONS:CFTR disruption leads to increased myocardial contractility at baseline, which may trigger untoward myocardial remodeling in CFpatients that is independent of lung diseases.
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