Functional cardiac consequences of β-adrenergic stress-induced injury in a model of Duchenne muscular dystrophy

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Date
2024
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American English
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The Company of Biologists
Abstract

Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD); however, in the mdx mouse model of DMD, the cardiac phenotype differs from that seen in DMD-associated cardiomyopathy. Although some have used pharmacologic stress to stimulate injury and enhance cardiac pathology in the mdx model, many methods lead to high mortality with variable cardiac outcomes, and do not recapitulate the structural and functional cardiac changes seen in human disease. Here, we describe a simple and effective method to enhance the cardiac phenotype model in mdx mice using advanced 2D and 4D high-frequency ultrasound to monitor cardiac dysfunction progression in vivo. mdx and wild-type mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathological assessment showed that isoproterenol treatment increased myocyte injury, elevated serum cardiac troponin I levels and enhanced fibrosis in mdx mice. Ultrasound revealed reduced ventricular function, decreased wall thickness, increased volumes and diminished cardiac reserve in mdx compared to wild-type mice. Our findings highlight the utility of challenging mdx mice with low-dose isoproterenol as a valuable model for exploring therapies targeting DMD-associated cardiac pathologies.

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Earl CC, Javier AJ, Richards AM, Markham LW, Goergen CJ, Welc SS. Functional cardiac consequences of β-adrenergic stress-induced injury in a model of Duchenne muscular dystrophy. Dis Model Mech. 2024;17(10):dmm050852. doi:10.1242/dmm.050852
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Disease Models & Mechanisms
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PMC
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