Journal article
Diminazene Aceturate Improves Cardiac Fibrosis and Diastolic Dysfunction in Rats with Kidney Disease
Elena Velkoska, Sheila K Patel, Karen Griggs, Louise M Burrell
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2016
Abstract
Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II. In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity. We hypothesised that diminazene aceturate (DIZE), which has been described as having an off-target effect to activate ACE2, would have beneficial cardiac effects in STNx rats. STNx led to hypertension, diastolic dysfunction, left ventricular hypertrophy, cardiac fibrosis, and increased cardiac ACE, ACE2, Ang II and Ang 1-7 levels. Cardiac gene expression of ADAM17 was also increased. In STNx, two-weeks of subcutaneous DIZE (15mg/kg/d) ..
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Grants
Awarded by National Health and Medical Research Council of Australia
Funding Acknowledgements
This work was supported by funding granted to EV from National Health and Medical Research Council of Australia (APP1048285).