Document Detail

Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy.
MedLine Citation:
PMID:  14715896     Owner:  NLM     Status:  MEDLINE    
One of the hallmarks of cardiomyopathy and heart failure is pronounced and progressive cardiomyocyte death. Understanding the mechanisms involved in cardiomyocyte cell death is a topic of great interest for treatment of cardiac disease. Mice null for desmin, the muscle-specific member of the intermediate filament gene family, develop cardiomyopathy characterized by extensive cardiomyocyte death, fibrosis, calcification, and eventual heart failure. The earliest ultrastructural defects are observed in mitochondria. In the present study, we have demonstrated that these mitochondrial abnormalities are the primary cause of the observed cardiomyopathy and that these defects can be ameliorated by overexpression of bcl-2 in desmin null heart. Overexpression of bcl-2 in the desmin null heart results in correction of mitochondrial defects, reduced occurrence of fibrotic lesions in the myocardium, prevention of cardiac hypertrophy, restoration of cardiomyocyte ultrastructure, and significant improvement of cardiac function. Furthermore, we have found that loss of desmin also diminishes the capacity of mitochondria to resist exposure to calcium, a defect that can be partially restored by bcl-2 overexpression. These results point to a unique function for desmin in protection of mitochondria from calcium exposure that can be partially rescued by overexpression of bcl-2. We show that bcl-2 cardiac overexpression has provided significant improvement of an inherited form of cardiomyopathy, revealing the potential for bcl-2, and perhaps other genes in the family, as therapeutic agents for heart disease of many types, including inherited forms.
Noah Weisleder; George E Taffet; Yassemi Capetanaki
Related Documents :
16804296 - Cardiac arrest and ventricular tachycardia in japanese-type apical hypertrophic cardiom...
15999476 - How a left-to-right shunt may protect against haemodynamic deterioration in restrictive...
3552306 - Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts,...
11455396 - Distinguishing cardiac features of a novel form of congenital muscular dystrophy (salih...
7634466 - Glibenclamide, a selective inhibitor of atp-sensitive k+ channels, attenuates metabolic...
9832116 - Usefulness of echocardiographic determined tricuspid regurgitation in predicting event-...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-01-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  101     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-21     Completed Date:  2004-03-01     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  769-74     Citation Subset:  IM    
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Calcinosis / pathology
Calcium / pharmacology
Cardiomyopathy, Hypertrophic, Familial / genetics*,  pathology,  therapy*
Desmin / deficiency*,  genetics
Gene Expression
Genes, bcl-2*
Genetic Therapy
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Electron
Mitochondrial Diseases / genetics*,  pathology,  therapy*
Mitochondrial Swelling / drug effects
Myocardium / pathology
Organ Size
Grant Support
Reg. No./Substance:
0/Desmin; 7440-70-2/Calcium

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

Previous Document:  Maintaining your immune system--one method for enhanced longevity.
Next Document:  The HcrVf2 gene from a wild apple confers scab resistance to a transgenic cultivated variety.