Modulation of caveolins, integrins and plasma membrane repair proteins in anthracycline-induced heart failure in rabbits

PLoS One. 2017 May 12;12(5):e0177660. doi: 10.1371/journal.pone.0177660. eCollection 2017.


Anthracyclines are chemotherapeutic drugs known to induce heart failure in a dose-dependent manner. Mechanisms involved in anthracycline cardiotoxicity are an area of relevant investigation. Caveolins bind, organize and regulate receptors and signaling molecules within cell membranes. Caveolin-3 (Cav-3), integrins and related membrane repair proteins can function as cardioprotective proteins. Expression of these proteins in anthracycline-induced heart failure has not been evaluated. We tested the hypothesis that daunorubicin alters cardioprotective protein expression in the heart. Rabbits were administered daunorubicin (3 mg/kg, IV) weekly, for three weeks or nine weeks. Nine weeks but not three weeks of daunorubicin resulted in progressive reduced left ventricular function. Cav-3 expression in the heart was unchanged at three weeks of daunorubicin and increased in nine week treated rabbits when compared to control hearts. Electron microscopy showed caveolae in the heart were increased and mitochondrial number and size were decreased after nine weeks of daunorubicin. Activated beta-1 (β1) integrin and the membrane repair protein MG53 were increased after nine weeks of daunorubicin vs. controls with no change at the three week time point. The results suggest a potential pathophysiological role for Cav3, integrins and membrane repair in daunorubicin-induced heart failure.

MeSH terms

  • Animals
  • Anthracyclines / toxicity*
  • Blotting, Western
  • Cardiotoxicity / blood
  • Cardiotoxicity / metabolism
  • Caveolins / metabolism*
  • Cholesterol / blood
  • Cholesterol / metabolism
  • Daunorubicin / toxicity*
  • Echocardiography
  • Heart Failure / chemically induced
  • Heart Failure / metabolism*
  • Immunohistochemistry
  • Integrins / metabolism*
  • Microscopy, Electron
  • Myocardium / metabolism
  • Myocardium / pathology
  • Rabbits


  • Anthracyclines
  • Caveolins
  • Integrins
  • Cholesterol
  • Daunorubicin