Document Detail

Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.
MedLine Citation:
PMID:  22427904     Owner:  NLM     Status:  MEDLINE    
Duchenne muscular dystrophy (DMD) is a progressive and fatal disease of muscle wasting caused by loss of the cytoskeletal protein dystrophin. In the heart, DMD results in progressive cardiomyopathy and dilation of the left ventricle through mechanisms that are not fully understood. Previous reports have shown that loss of dystrophin causes sarcolemmal instability and reduced mechanical compliance of isolated cardiac myocytes. To expand upon these findings, here we have subjected the left ventricles of dystrophin-deficient mdx hearts to mechanical stretch. Unexpectedly, isolated mdx hearts showed increased left ventricular (LV) compliance compared to controls during stretch as LV volume was increased above normal end diastolic volume. During LV chamber distention, sarcomere lengths increased similarly in mdx and WT hearts despite greater excursions in volume of mdx hearts. This suggests that the mechanical properties of the intact heart cannot be modeled as a simple extrapolation of findings in single cardiac myocytes. To explain these findings, a model is proposed in which disruption of the dystrophin-glycoprotein complex perturbs cell-extracellular matrix contacts and promotes the apparent slippage of myocytes past each other during LV distension. In comparison, similar increases in LV compliance were obtained in isolated hearts from β-sarcoglycan-null and laminin-α(2) mutant mice, but not in dysferlin-null mice, suggesting that increased whole-organ compliance in mdx mice is a specific effect of disrupted cell-extracellular matrix contacts and not a general consequence of cardiomyopathy via membrane defect processes. Collectively, these findings suggest a novel and cell-death independent mechanism for the progressive pathological LV dilation that occurs in DMD.
Matthew S Barnabei; Joseph M Metzger
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-09
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-03-19     Completed Date:  2012-08-20     Revised Date:  2014-06-24    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e32880     Citation Subset:  IM    
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MeSH Terms
Analysis of Variance
Compliance / physiology
Dystrophin / deficiency*
Fluorescent Antibody Technique
L-Lactate Dehydrogenase / metabolism
Laminin / deficiency
Membrane Proteins / deficiency
Mice, Inbred mdx
Microscopy, Confocal
Models, Biological*
Muscular Dystrophy, Duchenne / physiopathology*
Myocytes, Cardiac / chemistry*
Physical Stimulation
Sarcoglycans / deficiency
Sarcomeres / physiology
Stress, Mechanical
Ventricular Function, Left / physiology*
Grant Support
5R01-AG034107-02/AG/NIA NIH HHS; R01 HL059301/HL/NHLBI NIH HHS; T32 GM008322/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Dysf protein, mouse; 0/Dystrophin; 0/Laminin; 0/Membrane Proteins; 0/Sarcoglycans; 0/laminin alpha 2; EC Dehydrogenase

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

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