The impact of Cystic Fibrosis Transmembrane Regulator Disruption on cardiac function and stress response

Kai Jiang; Sen Jiao; Megan Vitko; Rebecca Darrah; Chris A Flask; Craig A Hodges; Xin Yu

doi:10.1016/j.jcf.2015.06.003

The impact of Cystic Fibrosis Transmembrane Regulator Disruption on cardiac function and stress response

J Cyst Fibros. 2016 Jan;15(1):34-42. doi: 10.1016/j.jcf.2015.06.003. Epub 2015 Jun 25.

Authors

Kai Jiang¹, Sen Jiao¹, Megan Vitko², Rebecca Darrah², Chris A Flask³, Craig A Hodges⁴, Xin Yu⁵

Affiliations

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.

Keywords: CFTR; cardiac myocyte; cystic fibrosis; left ventricular function; β-adrenergic stimulation.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adrenergic beta-1 Receptor Agonists / pharmacology
Animals
Aorta / pathology
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
Cystic Fibrosis* / metabolism
Cystic Fibrosis* / physiopathology
Dobutamine / pharmacology*
Heart* / drug effects
Heart* / physiopathology
Magnetic Resonance Imaging
Mice
Mice, Inbred CFTR
Mice, Knockout
Myocytes, Cardiac* / drug effects
Myocytes, Cardiac* / metabolism
Organ Size
Stimulation, Chemical
Ventricular Remodeling*

Substances

Adrenergic beta-1 Receptor Agonists
Cystic Fibrosis Transmembrane Conductance Regulator
Dobutamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding