Journal article
Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury
The Journal of clinical investigation, Vol.117(7), pp.1805-1813
07/02/2007
DOI: 10.1172/JCI30848
PMCID: PMC1904311
PMID: 17607357
Abstract
Dilated cardiomyopathy is a life-threatening syndrome that can arise from a myriad of causes, but predisposition toward this malady is inherited in many cases. A number of inherited forms of dilated cardiomyopathy arise from mutations in genes that encode proteins involved in linking the cytoskeleton to the extracellular matrix, and disruption of this link renders the cell membrane more susceptible to injury. Membrane repair is an important cellular mechanism that animal cells have developed to survive membrane disruption. We have previously shown that dysferlin deficiency leads to defective membrane resealing in skeletal muscle and muscle necrosis; however, the function of dysferlin in the heart remains to be determined. Here, we demonstrate that dysferlin is also involved in cardiomyocyte membrane repair and that dysferlin deficiency leads to cardiomyopathy. In particular, stress exercise disturbs left ventricular function in
dysferlin
-null mice and increases Evans blue dye uptake in dysferlin-deficient cardiomyocytes. Furthermore, a combined deficiency of dystrophin and dysferlin leads to early onset cardiomyopathy. Our results suggest that dysferlin-mediated membrane repair is important for maintaining membrane integrity of cardiomyocytes, particularly under conditions of mechanical stress. Thus, our study establishes what we believe is a novel mechanism underlying the cardiomyopathy that results from a defective membrane repair in the absence of dysferlin.
Details
- Title: Subtitle
- Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury
- Creators
- Renzhi Han - Howard Hughes Medical InstituteDimple Bansal - Howard Hughes Medical InstituteKatsuya Miyake - Howard Hughes Medical InstituteViviane P Muniz - Howard Hughes Medical InstituteRobert M Weiss - Howard Hughes Medical InstitutePaul L McNeil - Howard Hughes Medical InstituteKevin P Campbell - Howard Hughes Medical Institute
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.117(7), pp.1805-1813
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI30848
- PMID
- 17607357
- PMCID
- PMC1904311
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 07/02/2007
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984020868202771
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