title: Myocardial oxidative stress, osteogenic phenotype, and energy metabolism are differentially involved in the initiation and early progression of delta-sarcoglycan-null cardiomyopathy.
abstract: Dilated cardiomyopathy (DCM) is a common cause of heart failure, and identification of early pathogenic events occurring prior to the onset of cardiac dysfunction is of mechanistic, diagnostic, and therapeutic importance. The work characterized early biochemical pathogenesis in TO2 strain hamsters lacking delta-sarcoglycan. Although the TO2 hamster heart exhibits normal function at 1 month of age (presymptomatic stage), elevated levels of myeloperoxidase, monocyte chemotactic protein-1, malondialdehyde, osteopontin, and alkaline phosphatase were evident, indicating the presence of inflammation, oxidative stress, and osteogenic phenotype. These changes were localized primarily to the myocardium. Derangement in energy metabolism was identified at the symptomatic stage (4 month), and is marked by attenuated activity and expression of pyruvate dehydrogenase E1 subunit, which catalyzes the rate-limiting step in aerobic glucose metabolism. Thus, this study illustrates differential involvement of oxidative stress, osteogenic phenotype, and glucose metabolism in the initiation and early progression of delta-sarcoglycan-null DCM.
authors: Department of Biochemistry and Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, NY 14214, USA.
authors: Comlan
authors: C
authors: Missihoun
authors: David
authors: D
authors: Zisa
authors: Arsalan
authors: A
authors: Shabbir
authors: Huey
authors: H
authors: Lin
authors: Techung
authors: T
authors: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006224:Cricetinae; D003412:Cricetulus; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology*; D018384:Oxidative Stress; D010641:Phenotype; D021122:Protein Subunits / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D049031:Sarcoglycans / Q000235:genetics / Q000378:metabolism; D014020:Tissue Extracts / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007328:Insulin; D020738:Leptin; D021122:Protein Subunits; D011768:Pyruvate Dehydrogenase Complex; D049031:Sarcoglycans; D014020:Tissue Extracts; D005947:Glucose