Liver‐Targeted Angiotensin Converting Enzyme 2 Therapy Inhibits Chronic Biliary Fibrosis in Multiple Drug‐Resistant Gene 2‐Knockout Mice

There is a large unmet need for effective therapies for cholestatic disorders, including primary sclerosing cholangitis (PSC), a disease that commonly results in liver failure. Angiotensin (Ang) II of the renin Ang system (RAS) is a potent profibrotic peptide, and Ang converting enzyme 2 (ACE2) of t...

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Bibliographic Details
Published in:Hepatology communications 2019-12, Vol.3 (12), p.1656-1673
Main Authors: Rajapaksha, Indu G., Gunarathne, Lakmie S., Asadi, Khashayar, Cunningham, Sharon C., Sharland, Alexandra, Alexander, Ian E., Angus, Peter W., Herath, Chandana B.
Format: Article
Language:English
Subjects:
Age
Animals
Bile
Cytokines
Enzymes
Gallbladder diseases
Gene therapy
Growth factors
Histology
Liver diseases
Medical research
Original
Pathogenesis
Peptides
Phosphatase
Smooth muscle
Studies
Vectors (Biology)
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Summary:There is a large unmet need for effective therapies for cholestatic disorders, including primary sclerosing cholangitis (PSC), a disease that commonly results in liver failure. Angiotensin (Ang) II of the renin Ang system (RAS) is a potent profibrotic peptide, and Ang converting enzyme 2 (ACE2) of the alternate RAS breaks down Ang II to antifibrotic peptide Ang‐(1‐7). In the present study, we investigated long‐term effects of ACE2 delivered by an adeno‐associated viral vector and short‐term effects of Ang‐(1‐7) peptide in multiple drug‐resistant gene 2‐knockout (Mdr2‐KO) mice. These mice develop progressive biliary fibrosis with pathologic features closely resembling those observed in PSC. A single intraperitoneal injection of ACE2 therapy markedly reduced liver injury (P 
ISSN:2471-254X
2471-254X
DOI:10.1002/hep4.1434