| Secondary coronary artery vasospasm promotes cardiomyopathy progression. | |
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MedLine Citation:
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PMID: 14982859 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Genetic defects in the plasma membrane-associated sarcoglycan complex produce cardiomyopathy characterized by focal degeneration. The infarct-like pattern of cardiac degeneration has led to the hypothesis that coronary artery vasospasm underlies cardiomyopathy in this disorder. We evaluated the coronary vasculature of gamma-sarcoglycan mutant mice and found microvascular filling defects consistent with arterial vasospasm. However, the vascular smooth muscle sarcoglycan complex was intact in the coronary arteries of gamma-sarcoglycan hearts with perturbation of the sarcoglycan complex only within the adjacent myocytes. Thus, in this model, coronary artery vasospasm derives from a vascular smooth muscle-cell extrinsic process. To reduce this secondary vasospasm, we treated gamma-sarcoglycan-deficient mice with the calcium channel antagonist verapamil. Verapamil treatment eliminated evidence of vasospasm and ameliorated histological and functional evidence of cardiomyopathic progression. Echocardiography of verapamil-treated, gamma-sarcoglycan-null mice showed an improvement in left ventricular fractional shortening (44.3 +/- 13.3% treated versus 37.4 +/- 15.3% untreated), maximal velocity at the aortic outflow tract (114.9 +/- 27.9 cm/second versus 92.8 +/- 22.7 cm/second), and cardiac index (1.06 +/- 0.30 ml/minute/g versus 0.67 +/- 0.16 ml/minute/g, P < 0.05). These data indicate that secondary vasospasm contributes to the development of cardiomyopathy and is an important therapeutic target to limit cardiomyopathy progression. |
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Authors:
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Matthew T Wheeler; Claudia E Korcarz; Keith A Collins; Karen A Lapidos; Andrew A Hack; Matthew R Lyons; Sara Zarnegar; Judy U Earley; Roberto M Lang; Elizabeth M McNally |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of pathology Volume: 164 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-02-25 Completed Date: 2004-03-31 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1063-71 Citation Subset: AIM; IM |
Affiliation:
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Department of Molecular Genetics and Cell Biology, Section of Cardiology, University of Chicago, Chicago, Illinois, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium Channel Blockers / pharmacology Cardiomyopathies / drug therapy, etiology*, pathology* Coronary Vasospasm / complications*, drug therapy, physiopathology* Cytoskeletal Proteins / deficiency, genetics Disease Models, Animal Disease Progression Echocardiography Fluorescent Antibody Technique Heart / drug effects Heart Function Tests / drug effects Immunoblotting Membrane Glycoproteins / deficiency, genetics Mice Mice, Mutant Strains Muscle, Smooth, Vascular / drug effects, pathology Myocardium / pathology Sarcoglycans Verapamil / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL61322/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channel Blockers; 0/Cytoskeletal Proteins; 0/Membrane Glycoproteins; 0/Sarcoglycans; 52-53-9/Verapamil |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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