title: Sarcolemmal fragility secondary to the degradation of dystrophin in dilated cardiomyopathy, as estimated by electron microscopy.
abstract: A common gene deletion or mutation of delta-sarcoglycan (delta-SG) in dystrophin-related proteins (DRPs) is identified in both TO-2 strain hamsters and human families with dilated cardiomyopathy. We have succeeded in the long-lasting in vivo supplementation of a normal delta-SG gene by recombinant adeno-associated virus vector, restoration of the morphological and functional degeneration, and improvement in the prognosis of the TO-2 hamster. To evaluate the integrity of the sarcolemma (SL) and the subsequent change of organelles in cardiomyocytes of the TO-2 strain hamster, we examined electron microscopy (EM) images focusing on the sarcolemmal stability at the end stage of heart failure. Two types of sarcolemmal degradation were detected: the widened and locally thickened SL, and blurred and discontinuous SL. Bizarrely formed mitochondria of varying sizes were also observed. Immuno-EM revealed clear expression of dystrophin in the SL and intense expression at the costamere as well as at the T-tubules in the control F1B strain hearts, but a patchy deposition of dystrophin was observed along the SL without the transgene of delta-SG. In contrast to the previous reports that dystrophin's integrity was intact, the present results suggest that the gene deletion of delta-SG and the loss of delta-SG protein in the SL cardioselectively cause the morphological and functional deterioration of dystrophin and the resultant instability of the SL. The sarcolemmal fragility may be similar to Duchenne-type progressive muscular dystrophy in skeletal muscle. In addition to the mechanical role, another aspect of DRPs for the intracellular signal transmission is also discussed.
authors.affiliation: Division of Pharmacy, Niigata University of Medical Hospital, Niigata University School of Medicine, Niigata, Japan;
authors.forename: Tomie
authors.initials: T
authors.lastname: Kawada
authors.forename: Chieko
authors.initials: C
authors.lastname: Hemmi
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuda
authors.forename: Asaki
authors.initials: A
authors.lastname: Tezuka
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Iwasawa
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Toyo-Oka