Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex

Ronald D Cohn; Madeleine Durbeej; Steven A Moore; Ramón Coral-Vazquez; Sally Prouty; Kevin P Campbell

doi:10.1172/JCI11642

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Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex

Journal article

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Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex

Ronald D Cohn, Madeleine Durbeej, Steven A Moore, Ramón Coral-Vazquez, Sally Prouty and Kevin P Campbell

The Journal of clinical investigation, Vol.107(2), pp.R1-R7

01/15/2001

DOI: 10.1172/JCI11642

PMCID: PMC199179

PMID: 11160141

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Abstract

Cardiomyopathy is a multifactorial disease, and the dystrophin-glycoprotein complex has been implicated in the pathogenesis of both hereditary and acquired forms of the disease. Using mouse models of cardiomyopathy made by ablating genes for components of the sarcoglycan complex, we show that long-term treatment with verapamil, a calcium channel blocker with vasodilator properties, can alleviate the severe cardiomyopathic phenotype, restoring normal serum levels for cardiac troponin I and normal cardiac muscle morphology. Interruption of verapamil treatment leads again to vascular dysfunction and acute myocardial necrosis, indicating that predilection for cardiomyopathy is a continuing process. In contrast, verapamil did not prevent cardiac muscle pathology in dystrophin-deficient mdx mice, which neither show a disruption of the sarcoglycan complex in vascular smooth muscle nor vascular dysfunction. Hence, our data strongly suggest that pharmacological intervention with verapamil merits investigation as a potential therapeutic option not only for patients with sarcoglycan mutations, but also for patients with idiopathic cardiomyopathy associated with myocardial ischemia not related to atherosclerotic coronary artery disease.

Details

Title: Subtitle: Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex
Creators: Ronald D Cohn - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, and
Madeleine Durbeej - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, and
Steven A Moore - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, and
Ramón Coral-Vazquez - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, and
Sally Prouty - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, and
Kevin P Campbell - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, and
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.107(2), pp.R1-R7
Publisher: American Society for Clinical Investigation
DOI: 10.1172/JCI11642
PMID: 11160141
PMCID: PMC199179
ISSN: 0021-9738
eISSN: 1558-8238
Language: English
Date published: 01/15/2001
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute
Record Identifier: 9984020898002771

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