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Am J Physiol Heart Circ Physiol 278: H1362-H1370, 2000;
0363-6135/00 $5.00
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Vol. 278, Issue 4, H1362-H1370, April 2000

Altered membrane proteins and permeability correlate with cardiac dysfunction in cardiomyopathic hamsters

Yasuhiro Ikeda1, Maryann Martone2, Yusu Gu1, Masahiko Hoshijima1, Andrea Thor2, Sam S. Oh1, Kirk L. Peterson1, and John Ross Jr.1

1 Division of Cardiology, Department of Medicine, and 2 Department of Neurosciences, University of California, San Diego, La Jolla, California 92093-0613

A mutation in the delta -sarcoglycan (SG) gene with absence of delta -SG protein in the heart has been identified in the BIO14.6 cardiomyopathic (CM) hamster, but how the defective gene leads to myocardial degeneration and dysfunction is unknown. We correlated left ventricular (LV) function with increased sarcolemmal membrane permeability and investigated the LV distribution of the dystrophin-dystroglycan complex in BIO14.6 CM hamsters. On echocardiography at 5 wk of age, the CM hamsters showed a mildly enlarged diastolic dimension (LVDD) with decreased LV percent fractional shortening (%FS), and at 9 wk further enlargement of LVDD with reduction of %FS was observed. The percent area of myocardium exhibiting increased membrane permeability or membrane rupture, assessed by Evans blue dye (EBD) staining and wheat germ agglutinin, was greater at 9 than at 5 wk. In areas not stained by EBD, immunostaining of dystrophin was detected in CM hamsters at sarcolemma and T tubules, as expected, but it was also abnormally expressed at the intercalated discs; in addition, the expression of beta -dystroglycan was significantly reduced compared with control hearts. As previously described, alpha -SG was completely deficient in CM hearts compared with control hearts. In myocardial areas showing increased sarcolemmal permeability, neither dystrophin nor beta -dystroglycan could be identified by immunolabeling. Thus, together with the known loss of delta -SG and other SGs, abnormal distribution of dystrophin and reduction of beta -dystroglycan are associated with increased sarcolemmal permeability followed by cell rupture, which correlates with early progressive cardiac dysfunction in the BIO14.6 CM hamster.

delta -sarcoglycan; dystrophin-dystroglycan complex; heart failure; Evans blue dye


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