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Blunted cardiac beta-adrenergic response as an early indication of cardiac dysfunction in Duchenne muscular dystrophy
Journal article   Open access   Peer reviewed

Blunted cardiac beta-adrenergic response as an early indication of cardiac dysfunction in Duchenne muscular dystrophy

Ying Li, Shuai Zhang, Xiaoying Zhang, Jing Li, Xiaojie Ai, Li Zhang, Daohai Yu, Shuping Ge, Yizhi Peng and Xiongwen Chen
Cardiovascular research, v 103(1), pp 60-71
01 Jul 2014
DOI: https://doi.org/10.1093/cvr/cvu119
PMID: 24812281
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1093/cvr/cvu119View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Cardiac & Cardiovascular Systems Cardiovascular System & Cardiology Life Sciences & Biomedicine Science & Technology
To determine whether altered beta-adrenergic responses contribute to early cardiac dysfunction in mdx (X-linked muscular dystrophy) mice, an animal model for human Duchenne muscular dystrophy. Replacement fibrosis in mdx hearts gradually increased with age, suggesting a gradual loss of cardiomyocytes. Echocardiography and intra-left ventricular haemodynamic measurements detected baseline cardiac dysfunction in mdx mice at a parts per thousand yen8 months. However, a reduction of cardiac beta-adrenergic response to isoproterenol (ISO) was already present in mdx mice at 4 months. Ventricular myocytes (VMs) isolated from 4- and 8-month-old mdx mice had greater baseline contractile function {fractional shortening, [Ca2+](i), and sarcoplasmic reticulum (SR) Ca2+ content} and ICa-L than age-matched control VMs and than myocytes isolated from 2-month-old mdx mice. ISO increased myocyte function in the VMs of 4- and 8-month-old mdx mice to the same level as in age-matched control VMs. In the VMs of 12-month-old mdx mice, ISO failed to increase myocyte function to the level in VMs of 12-month-old control mice and could not further increaseI(Ca-L). No differences were observed in the expression of Cav1.2 alpha 1c, Cav1.2 beta 1, Cav1.2 beta 2, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), and the Na+/Ca2+ exchanger. In contrast, total ryanodine receptor 2 (RyR2) and basal phosphorylation of RyR2, phospholamban, and Cav1.2 alpha 1c were found to be increased in hearts of 4-month-old mdx mice; baseline protein kinase A activity was also increased. After ISO treatment, phosphorylation levels were the same in mdx and control hearts. VMs of 4-month-old mdx mice had reduced beta1-adrenergic receptor (beta 1-AR) density and beta-adrenergic sensitivity. In young mdx mice, the myocyte increases its contractile function to compensate for myocyte loss. However, these myocytes with enhanced baseline function have reduced potential for stimulation, decreased beta 1-AR density/sensitivity, leading to blunted cardiac beta-adrenergic response.

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Web of Science research areas
Cardiac & Cardiovascular Systems
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