Document Detail

Secondary coronary artery vasospasm promotes cardiomyopathy progression.
MedLine Citation:
PMID:  14982859     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of pathology     Volume:  164     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-02-25     Completed Date:  2004-03-31     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1063-71     Citation Subset:  AIM; IM    
Department of Molecular Genetics and Cell Biology, Section of Cardiology, University of Chicago, Chicago, Illinois, USA.
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MeSH Terms
Calcium Channel Blockers / pharmacology
Cardiomyopathies / drug therapy,  etiology*,  pathology*
Coronary Vasospasm / complications*,  drug therapy,  physiopathology*
Cytoskeletal Proteins / deficiency,  genetics
Disease Models, Animal
Disease Progression
Fluorescent Antibody Technique
Heart / drug effects
Heart Function Tests / drug effects
Membrane Glycoproteins / deficiency,  genetics
Mice, Mutant Strains
Muscle, Smooth, Vascular / drug effects,  pathology
Myocardium / pathology
Verapamil / pharmacology
Grant Support
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Cytoskeletal Proteins; 0/Membrane Glycoproteins; 0/Sarcoglycans; 52-53-9/Verapamil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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