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

Research output: Contribution to journalArticlepeer-review

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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