Distinct roles for angiotensin‐converting enzyme 2 and carboxypeptidase A in the processing of angiotensins within the murine heart
Key result
In the murine heart, ACE2 is the primary pathway for metabolizing Ang II to Ang(1-7), while carboxypeptidase A primarily converts Ang I to Ang(1-9).
Population
Wild-type (WT), ACE null (ACE(-/-)), and ACE2 null (ACE2(-/-)) murine heart membranes
Comparison
ACE2 inhibitor MLN4760 and carboxypeptidase A… vs Baseline/untreated cardiac membranes across the…
Design
Preclinical
Authors
Discussion
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Implication
Cautions against extrapolating murine cardiac angiotensin pathways to humans; leaves open their role in clinical remodeling or therapy.
Structured PICO
P
Population
Wild-type, ACE(-/-), and ACE2(-/-) mice used to study the metabolism of angiotensins in the murine heart.
I
Intervention
ACE2 inhibitor MLN4760 and carboxypeptidase A inhibitor benzylsuccinate
C
Comparator
Baseline/untreated cardiac membranes across the different mouse strains
O
Outcome
Metabolism of Angiotensin I and Angiotensin II, and generation of Ang(1-7) and Ang(1-9)surrogate
In the murine heart, ACE2 is the primary pathway for metabolizing Ang II to the antifibrotic peptide Ang(1-7), whereas carboxypeptidase A converts Ang I to Ang(1-9).
Cite This Study
Garabelli et al. (2008) studied Angiotensin metabolism in murine heart. ACE2 and carboxypeptidase A inhibition/knockout vs. Wild-type was evaluated on Generation of Ang(1-7) from Ang II and Ang(1-9) from Ang I. In the murine heart, ACE2 is the primary pathway for metabolizing Ang II to Ang(1-7), while carboxypeptidase A primarily converts Ang I to Ang(1-9).