A new paradigm for the progression of advanced heart failure.
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Accession number;04A0131238
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| Title;A new paradigm for the progression of advanced heart failure. |
| Author;
KAWADA TOMIE
(Niigata Univ., JPN)
NAKAZAWA MIKIO
(Niigata Univ., Fac. Medicine, JPN)
TOYOOKA TERUHIKO
(Univ. of Tokyo, Fac. of Med.)
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Journal Title;Folia Pharmacologica Japonica
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Journal Code:G0740A
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ISSN:0015-5691
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VOL.123;NO.2;PAGE.55-62(2004)
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| Figure&Table&Reference;FIG.5, REF.29 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;To clarify the precise mechanism for the progression of advanced heart failure (AdHF), we assessed the scheme in two HF models, using (I) TO-2 strain hamsters sharing common genetic and clinical features to human families with the .DELTA.-sarcoglycan (SG) gene mutation and (II) administration of a high-dose (HD) of isoproterenol (Isp) to normal rats. .DELTA.-SG is a component in dystrophin (Dys)-related proteins that stabilize the sarcolemma (SL) during repeated heart beats. In TO-2, we followed time course of hemodynamics, immunostaining and Western blotting of Dys and in situ SL permeability by Evans blue uptake with or without the gene therapy. Dys was age-dependently translocated from the SL to myoplasm (MP) where the SL instability accompanied the fragmention of Dys. By gene therapy to supplement the normal .DELTA.-SG gene in hearts in vivo, we found that Dys translocation was selectively improved in cardiomyocytes expressing the .DELTA.-SG transgene, where the SL fragility was ameliorated. Most importantly, the survival period of the animals was prolonged. Furthermore, Dys but not .DELTA.-SG was also time-dependently shifted with a HD of Isp from the SL to MP and fragmented, while .DELTA.-SG was preserved intact. We present a novel paradigm that disruption of Dys, but not .DELTA.-SG per se, leads to AdHF irrespective of hereditary or acquired origin. (author abst.) |
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