Dystrophic heart failure blocked by membrane sealant poloxamer
dc.contributor.author | Yasuda, S. | en_US |
dc.contributor.author | Townsend, D. | en_US |
dc.contributor.author | Michele, D. E. | en_US |
dc.contributor.author | Favre, E. G. | en_US |
dc.contributor.author | Day, Sharlene | en_US |
dc.contributor.author | Metzger, Joseph M. | en_US |
dc.date.accessioned | 2009-06-01T17:32:47Z | |
dc.date.available | 2009-06-01T17:32:47Z | |
dc.date.issued | 2005-08-18 | en_US |
dc.identifier.citation | Yasuda, S; Townsend, D; Michele, DE; Favre, EG; Day, SM; Metzger, JM. (2005) "Dystrophic heart failure blocked by membrane sealant poloxamer." Nature 436(7053): 1025-1029. <http://hdl.handle.net/2027.42/62706> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62706 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16025101&dopt=citation | en_US |
dc.description.abstract | Dystrophin deficiency causes Duchenne muscular dystrophy (DMD) in humans, an inherited and progressive disease of striated muscle deterioration that frequently involves pronounced cardiomyopathy(1). Heart failure is the second leading cause of fatalities in DMD1,2. Progress towards defining the molecular basis of disease in DMD has mostly come from studies on skeletal muscle, with comparatively little attention directed to cardiac muscle. The pathophysiological mechanisms involved in cardiac myocytes may differ significantly from skeletal myofibres; this is underscored by the presence of significant cardiac disease in patients with truncated or reduced levels of dystrophin but without skeletal muscle disease(3). Here we show that intact, isolated dystrophin-deficient cardiac myocytes have reduced compliance and increased susceptibility to stretch-mediated calcium overload, leading to cell contracture and death, and that application of the membrane sealant poloxamer 188 corrects these defects in vitro. In vivo administration of poloxamer 188 to dystrophic mice instantly improved ventricular geometry and blocked the development of acute cardiac failure during a dobutamine-mediated stress protocol. Once issues relating to optimal dosing and long-term effects of poloxamer 188 in humans have been resolved, chemical-based membrane sealants could represent a new therapeutic approach for preventing or reversing the progression of cardiomyopathy and heart failure in muscular dystrophy. | en_US |
dc.format.extent | 396555 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/octet-stream | |
dc.format.mimetype | text/plain | |
dc.publisher | Nature Publishing Group | en_US |
dc.source | Nature | en_US |
dc.title | Dystrophic heart failure blocked by membrane sealant poloxamer | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA | en_US |
dc.identifier.pmid | 16025101 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62706/1/nature03844.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/nature03844 | en_US |
dc.identifier.source | Nature | en_US |
dc.contributor.authoremail | metzgerj@umich.edu | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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