Skip to main content

Open Access Akt-mTOR Pathway Inhibits Apoptosis and Fibrosis in Doxorubicin-Induced Cardiotoxicity Following Embryonic Stem Cell Transplantation

Download / Buy Article:
Open access content The full text is Open Access.
(PDF 781.1884765625 kb)


Doxorubicin (DOX) is an effective chemotherapeutic drug used for the treatment of a variety of malignancies. Unfortunately, time and dose-dependent DOX therapy induces cardiotoxicity and heart failure. We previously reported that transplanted embryonic stem(ES) cells and the conditioned medium (CM) can repair and regenerate injured myocardium in acute DOX induced cardiomyopathy (DIC). However, the effectiveness of ES cell and CM therapeutics has not been challenged in the chronic DIC model. To this end,the long term impact of ES cells and CM on apoptosis, fibrosis, cytoplasmic vacuolization, oxidative stress, and their associated mediators were examined. Fourweeks post-DIC, ES cell and CM transplanted hearts showed a significant decrease in cardiac apoptotic nuclei which was consequent to modulation of signaling molecules in the Akt pathway including PTEN, Akt, and mTOR. Cytoplasmic vacuolization was reduced following treatment with ES cells and CM as was cardiac fibrosis, which was attributable to down regulation of MMP-9 activity. Oxidative stress, as evidenced by DHE staining and lipid peroxide concentration,was significantly diminished and preservation of the antioxidant defense system was observed following CM and ES cell transplantation. In conclusion,our data suggest that transplanted ES cells and CM have long term potentiation to significantlymitigate various adverse pathological mechanisms present in the injured chronic DIC heart.


Appeared or available online: Mon Mar 03 00:00:00 GMT 2014

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more