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

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 ß-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 ß-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.