Alterations in dystrophin-related glycoproteins in development of right ventricular failure in rats

Takuya Daicho1, Yoriko Daisho, Suguru Kojima

  • 1Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Japan.

Insights

Genetic depletion of the dystrophin-related glycoprotein complex contributes to heart failure. This study found that alterations in this complex are linked to right ventricular failure in monocrotaline-induced rat cardiomyopathy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Animal Models of Disease

Background:

  • Genetic defects in the dystrophin-related glycoprotein (DRGP) complex are known to cause cardiomyopathy.
  • The role of DRGP alterations in right ventricular failure, particularly in models of pulmonary hypertension, requires further investigation.

Purpose of the Study:

  • To investigate the involvement of DRGP alterations in the development of right ventricular failure in monocrotaline-administered (MCT) rats.
  • To explore the potential mechanisms, including protease activity, underlying these DRGP changes.

Main Methods:

  • Rats were administered monocrotaline (60 mg/kg) subcutaneously.
  • Echocardiography was performed at 6 and 8 weeks to assess cardiac function.
  • Levels of alpha-sarcoglycan, beta-sarcoglycan, and beta-dystroglycan were measured in right ventricular tissue.
  • Activity and content of m-calpain and matrix metalloproteinase-2 were assessed in MCT rat right ventricles.

Main Results:

  • MCT rats exhibited decreased cardiac output indices and increased right ventricular Tei indices by 6 weeks, indicating right ventricular failure.
  • Significant decreases in alpha-sarcoglycan, beta-sarcoglycan, and beta-dystroglycan were observed in the right ventricles of MCT rats.
  • These DRGP component decreases were inversely correlated with the elevated right ventricular Tei index.
  • Increased content and activity of m-calpain and matrix metalloproteinase-2 were detected in the right ventricles of MCT rats.

Conclusions:

  • Alterations in the dystrophin-related glycoprotein complex are implicated in the pathogenesis of right ventricular failure in MCT rats.
  • Increased activity of m-calpain and/or matrix metalloproteinase-2 may mediate the degradation of DRGP components, contributing to right ventricular dysfunction.

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