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Potential beneficial effects of ACE2‐Ang‐(1–7) axis in doxorubicin‐induced cardiomyopathy
Author(s) -
Rathinasabapathy Anandharajan,
Bruce Erin,
Qi Yanfei,
Ma Sophia,
Raizada Mohan,
Katovich Michael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.848.5
Doxorubicin, one of the most effective chemotherapeutic agents, often leads to cardiomyopathy followed by congestive heart failure. Recent studies have shown that treatment with angiotensin II type 1 receptor antagonists (ARBs) and angiotensin converting enzyme inhibitors (ACEi) can attenuate doxorubicin‐induced cardiomyopathy. The use of ACEi and ARBs has been shown to increase production of ACE2 and Ang‐(1–7). We and others have previously demonstrated that an increased level of either ACE2 or Ang‐(1–7) is cardioprotective in several other models of heart disease. Therefore we investigated the role of this ACE2‐Ang‐(1–7) cardioprotective axis in doxorubicin‐induced cardiomyopathy. Preliminary in vitro studies have demonstrated that doxorubicin induces cell death in neonatal rat cardiomyoctyes in a dose dependent manner. Subsequent studies indicated that this cell death was mediated via apoptosis. Pre‐treatment of neonatal rat cardiomyocytes, with either Ang‐(1–7) or a putative activator of the ACE2‐Ang‐(1–7) axis, diminazene aceturate (DIZE), prevented this doxorubicin‐induced apoptosis. We are currently testing effects of Ang‐(1–7) in an animal model of doxorubicin‐induced cardiomyopathy. Collectively these results suggest that the ACE2‐Ang‐(1–7) axis is cardioprotective and elevation of this axis may prove beneficial in cancer patients treated with doxorubicin.