Myocardial oxidative stress, osteogenic phenotype, and energy metabolism are differentially involved in the initiation and early progression of delta-sarcoglycan-null cardiomyopathy

Mol Cell Biochem. 2009 Jan;321(1-2):45-52. doi: 10.1007/s11010-008-9908-0. Epub 2008 Aug 26.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / physiopathology*
  • Cricetinae
  • Cricetulus
  • Energy Metabolism*
  • Glucose / metabolism
  • Insulin / blood
  • Leptin / blood
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Osteogenesis / physiology*
  • Oxidative Stress*
  • Phenotype
  • Protein Subunits / metabolism
  • Pyruvate Dehydrogenase Complex / metabolism
  • Sarcoglycans* / genetics
  • Sarcoglycans* / metabolism
  • Tissue Extracts / metabolism

Substances

  • Biomarkers
  • Insulin
  • Leptin
  • Protein Subunits
  • Pyruvate Dehydrogenase Complex
  • Sarcoglycans
  • Tissue Extracts
  • Glucose