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

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• 作者：Kai Jiang^a ; ^f ; Sen Jiao^a ; ^f ; Megan Vitko^b ; Rebecca Darrah^b ; Chris A. Flask^a ; ^c ; ^d ; ^f ; Craig A. Hodges^b ; ^d ; Xin Yu^a ; ^c ; ^e ; ^f ; ^{xin.yu@case.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：cystic fibrosis ; CFTR ; left ventricular function ; β-adrenergic stimulation ; cardiac myocyte
• 刊名：Journal of Cystic Fibrosis
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：15
• 期：1
• 页码：34-42
• 全文大小：955 K

文摘

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 Ca^2 + 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 Ca^2 + 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.