Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury

Renzhi Han, Dimple Bansal, Katsuya Miyake, Viviane P. Muniz, Robert M. Weiss, Paul L. McNeil, Kevin P. Campbell

Research output: Contribution to journalArticle

114 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1805-1813
Number of pages9
JournalJournal of Clinical Investigation
Volume117
Issue number7
DOIs
StatePublished - Jul 2 2007

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Membranes
Wounds and Injuries
Cardiomyopathies
Cardiac Myocytes
Dilated Cardiomyopathy
Evans Blue
Dystrophin
Mechanical Stress
Cytoskeleton
Left Ventricular Function
Extracellular Matrix
Skeletal Muscle
Necrosis
Coloring Agents
Cell Membrane
Muscles
Mutation
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Han, R., Bansal, D., Miyake, K., Muniz, V. P., Weiss, R. M., McNeil, P. L., & Campbell, K. P. (2007). Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury. Journal of Clinical Investigation, 117(7), 1805-1813. https://doi.org/10.1172/JCI30848

Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury. / Han, Renzhi; Bansal, Dimple; Miyake, Katsuya; Muniz, Viviane P.; Weiss, Robert M.; McNeil, Paul L.; Campbell, Kevin P.

In: Journal of Clinical Investigation, Vol. 117, No. 7, 02.07.2007, p. 1805-1813.

Research output: Contribution to journalArticle

Han, R, Bansal, D, Miyake, K, Muniz, VP, Weiss, RM, McNeil, PL & Campbell, KP 2007, 'Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury', Journal of Clinical Investigation, vol. 117, no. 7, pp. 1805-1813. https://doi.org/10.1172/JCI30848
Han, Renzhi ; Bansal, Dimple ; Miyake, Katsuya ; Muniz, Viviane P. ; Weiss, Robert M. ; McNeil, Paul L. ; Campbell, Kevin P. / Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 7. pp. 1805-1813.
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