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Updated: May 15, 2026
Echocardiographic Assessment of the Right Heart in Mice
Published on: November 27, 2013
Left ventricular and aortic dysfunction in cystic fibrosis mice
Zachary M Sellers1, Attila Kovacs, Carla J Weinheimer
1College of Medicine, University of Illinois at Urbana-Champaign, United States. zsellers@stanford.edu
Insights
Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) mutation causes left ventricular remodeling and impaired heart function in mice, independent of lung disease. This highlights potential cardiovascular risks for aging CF patients.
Area of Science:
- Cardiovascular Physiology
- Genetic Diseases
- Pulmonary Medicine
Background:
- Left ventricular (LV) abnormalities are noted in cystic fibrosis (CF).
- The direct impact of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction on cardiac defects, separate from lung disease, is not fully understood.
Purpose of the Study:
- To investigate if CFTR mutation directly causes cardiac and aortic dysfunction.
- To assess cardiac and aortic function in a mouse model lacking functional CFTR but without lung disease.
Main Methods:
- Utilized gut-corrected F508del CFTR mutant mice (ΔF508) that do not develop human lung disease.
- Assessed in vivo heart and aortic function using 2D transthoracic echocardiography and LV catheterization.
- Evaluated cardiac reserve through β-adrenergic stimulation.
Main Results:
- ΔF508 mouse hearts exhibited LV concentric remodeling, enhanced inotropy, and greater lusitropy.
- Aortas showed increased stiffness and altered diastolic flow.
- β-adrenergic stimulation revealed a diminished cardiac reserve in mutant mice.
Conclusions:
- CFTR mutation induces LV remodeling and alters cardiac and aortic function in the absence of lung disease.
- Cardiovascular disease risk should be considered for cystic fibrosis patients as lifespans increase.
Background:
Left ventricular (LV) abnormalities have been reported in cystic fibrosis (CF); however, it remains unclear if loss of cystic fibrosis transmembrane conductance regulator (CFTR) function causes heart defects independent of lung disease.
Methods:
Using gut-corrected F508del CFTR mutant mice (ΔF508), which do not develop human lung disease, we examined in vivo heart and aortic function via 2D transthoracic echocardiography and LV catheterization.
Results:
ΔF508 mouse hearts showed LV concentric remodeling along with enhanced inotropy (increased +dP/dt, fractional shortening, decreased isovolumetric contraction time) and greater lusitropy (-dP/dt, Tau). Aortas displayed increased stiffness and altered diastolic flow. β-adrenergic stimulation revealed diminished cardiac reserve (attenuated +dP/dt,-dP/dt, LV pressure).
Conclusions:
In a mouse model of CF, CFTR mutation leads to LV remodeling with alteration of cardiac and aortic functions in the absence of lung disease. As CF patients live longer, more active lives, their risk for cardiovascular disease should be considered.
