title: Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex.
abstract: Cardiomyopathy is a multifactorial disease, and the dystrophin-glycoprotein complex has been implicated in the pathogenesis of both hereditary and acquired forms of the disease. Using mouse models of cardiomyopathy made by ablating genes for components of the sarcoglycan complex, we show that long-term treatment with verapamil, a calcium channel blocker with vasodilator properties, can alleviate the severe cardiomyopathic phenotype, restoring normal serum levels for cardiac troponin I and normal cardiac muscle morphology. Interruption of verapamil treatment leads again to vascular dysfunction and acute myocardial necrosis, indicating that predilection for cardiomyopathy is a continuing process. In contrast, verapamil did not prevent cardiac muscle pathology in dystrophin-deficient mdx mice, which neither show a disruption of the sarcoglycan complex in vascular smooth muscle nor vascular dysfunction. Hence, our data strongly suggest that pharmacological intervention with verapamil merits investigation as a potential therapeutic option not only for patients with sarcoglycan mutations, but also for patients with idiopathic cardiomyopathy associated with myocardial ischemia not related to atherosclerotic coronary artery disease.
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Cohn
authors.forename: M
authors.initials: M
authors.lastname: Durbeej
authors.forename: S A
authors.initials: SA
authors.lastname: Moore
authors.forename: R
authors.initials: R
authors.lastname: Coral-Vazquez
authors.forename: S
authors.initials: S
authors.lastname: Prouty
authors.forename: K P
authors.initials: KP
authors.lastname: Campbell
mesh_terms: D000367:Age Factors; D000818:Animals; D009202:Cardiomyopathies / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D002352:Carrier Proteins / Q000235:genetics; D003326:Coronary Circulation; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins; D049031:Sarcoglycans; D014336:Troponin / Q000097:blood; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D049031:Sarcoglycans; C491632:Sspn protein, mouse; D014336:Troponin; D014665:Vasodilator Agents; D014700:Verapamil