Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.

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...

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Autores principales:	Matthew S Barnabei, Joseph M Metzger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c821ddad9ba4c85a2088b9d2f066936
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spelling	oai:doaj.org-article:6c821ddad9ba4c85a2088b9d2f0669362021-11-18T07:25:37ZEx vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.1932-620310.1371/journal.pone.0032880https://doaj.org/article/6c821ddad9ba4c85a2088b9d2f0669362012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22427904/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Duchenne 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 BarnabeiJoseph M MetzgerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32880 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew S Barnabei Joseph M Metzger Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.
description	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.
format	article
author	Matthew S Barnabei Joseph M Metzger
author_facet	Matthew S Barnabei Joseph M Metzger
author_sort	Matthew S Barnabei
title	Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.
title_short	Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.
title_full	Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.
title_fullStr	Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.
title_full_unstemmed	Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.
title_sort	ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6c821ddad9ba4c85a2088b9d2f066936
work_keys_str_mv	AT matthewsbarnabei exvivostretchrevealsalteredmechanicalpropertiesofisolateddystrophindeficienthearts AT josephmmetzger exvivostretchrevealsalteredmechanicalpropertiesofisolateddystrophindeficienthearts
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Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.

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