Publication:

Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy (1999)

Author(s): Straub V; Barresi R; Coral-Vazquez R; Cohn RD; Moore SA; Hill JA; Weiss RM; Davisson RL; Bansal D; Hrstka RF; Williamson R; Campbell KP

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

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 alpha-sarcoglycan (Sgca) or delta-sarcoglycan (Sgcd). We found that only Sgcd null mice developed cardiomyopathy with focal areas of necrosis as the histological hallmark in cardiac and 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.

  • Short Title: Disruption of the sarcoglycan-sarcospan complex in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy
  • Date: 20-08-1999
  • Journal: Cell
  • Volume: 98
  • Issue: 4
  • Pages: 465-474
  • Publisher: Cell Press
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Animals Cardiomyopathy, Dilated/ genetics/metabolism/pathology Carrier Proteins/ physiology Coronary Vessels/pathology Cytoskeletal Proteins/deficiency/genetics/ physiology Macromolecular Substances Membrane Glycoproteins/deficiency/genetics/ physiology Membrane Proteins/ physiology Mice Mice, Knockout Muscle, Smooth, Vascular/ metabolism/pathology Muscular Dystrophy, Animal/ genetics/metabolism/pathology Myocardium/pathology Necrosis Neoplasm Proteins Physical Conditioning, Animal/adverse effects Sarcoglycans

Staff

Professor Volker Straub
Harold Macmillan Professor of Medicine