Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: A novel mechanism for cardiomyopathy and muscular dystrophy

Ramon Coral-Vazquez, Ronald D. Cohn, Steven A. Moore, Joseph A Hill, Robert M. Weiss, Robin L. Davisson, Volker Straub, Rita Barresi, Dimple Bansal, Ron F. Hrstka, Roger Williamson, Kevin P. Campbell

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Abstract

To investigate mechanisms in the pathogenesis of cardiomyopathy associated with mutations of the dystrophin-glycoprotein complex, we analyzed genetically engineered mice deficient for either α-sarcoglycan (Sgca) or δ- sarcoglycan (Sgcd). We found that only Sgcd null mice developed cardiomyopathy with focal areas of necrosis as the histological hallmark in cardiac end skeletal muscle. Absence of the sarcoglycan-sarcospan (SG-SSPN) complex in skeletal and cardiac membranes was observed in both animal models. Loss of vascular smooth muscle SG-SSPN complex was only detected in Sgcd null mice and associated with irregularities of the coronary vasculature. Administration of a vascular smooth muscle relaxant prevented onset of myocardial necrosis. Our data indicate that disruption of the SG-SSPN complex in vascular smooth muscle perturbs vascular function, which initiates cardiomyopathy and exacerbates muscular dystrophy.

Original languageEnglish (US)
Pages (from-to)465-474
Number of pages10
JournalCell
Volume98
Issue number4
DOIs
StatePublished - Aug 20 1999

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Coral-Vazquez, R., Cohn, R. D., Moore, S. A., Hill, J. A., Weiss, R. M., Davisson, R. L., Straub, V., Barresi, R., Bansal, D., Hrstka, R. F., Williamson, R., & Campbell, K. P. (1999). Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: A novel mechanism for cardiomyopathy and muscular dystrophy. Cell, 98(4), 465-474. https://doi.org/10.1016/S0092-8674(00)81975-3