Extensive induction of important mediators of fibrosis and dystrophic calcification in desmin-deficient cardiomyopathy

Am J Pathol. 2002 Mar;160(3):943-52. doi: 10.1016/S0002-9440(10)64916-4.


Mice lacking the intermediate filament protein desmin demonstrate abnormal mitochondria behavior, disruption of muscle architecture, and myocardial degeneration with extensive calcium deposits and fibrosis. These abnormalities are associated with cardiomyocyte hypertrophy, cardiac chamber dilation and eventually with heart failure. In an effort to elucidate the molecular mechanisms leading to the observed pathogenesis, we have analyzed gene expression changes in cardiac tissue using differential display polymerase chain reaction and cDNA atlas array methods. The most substantial changes were found in genes coding the small extracellular matrix proteins osteopontin and decorin that are dramatically induced in the desmin-null myocardium. We further analyzed their expression pattern both at the RNA and protein levels and we compared their spatial expression with the onset of calcification. Extensive osteopontin localization is observed by immunohistochemistry in the desmin-null myocardium in areas with massive myocyte death, as well as in hypercellular regions with variable degrees of calcification and fibrosis. Osteopontin is consistently co-localized with calcified deposits, which progressively are transformed to psammoma bodies surrounded by decorin, especially in the right ventricle. These data together with the observed up-regulation of transforming growth factor-beta1 and angiotensin-converting enzyme, could explain the extensive fibrosis and dystrophic calcification observed in the heart of desmin-null mice, potentially crucial events leading to heart failure.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcinosis* / genetics
  • Calcinosis* / metabolism
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism*
  • Cardiomyopathies / pathology
  • Decorin
  • Desmin / deficiency
  • Desmin / genetics*
  • Extracellular Matrix Proteins
  • Fibrosis
  • Gene Expression Regulation
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteopontin
  • Peptidyl-Dipeptidase A / biosynthesis
  • Proteoglycans / biosynthesis
  • Sialoglycoproteins / biosynthesis
  • Transforming Growth Factor beta / biosynthesis


  • Dcn protein, mouse
  • Decorin
  • Desmin
  • Extracellular Matrix Proteins
  • Proteoglycans
  • Sialoglycoproteins
  • Spp1 protein, mouse
  • Transforming Growth Factor beta
  • Osteopontin
  • Peptidyl-Dipeptidase A