Key result
Dogs with congestive heart failure had significantly higher median plasma ACE2 activity (6.9 vs 2.2 mU/mg; P=0.0003) and beneficial angiotensin peptides compared to healthy controls.
Why the study?
It was hypothesized that ACE2 is present in canine tissues and plasma, that equilibrium concentrations of RAAS angiotensin peptides differ in dogs with heart disease versus healthy dogs, and that rhACE2 alters these peptide concentrations.
Observational (n=83)
The ACE2 system is active in dogs with heart failure, and recombinant human ACE2 can favorably alter the balance of angiotensin peptides in vitro, highlighting a potential therapeutic target.
Answers are grounded in this paper and cite their sources.
ACE2 activity detectable with altered RAAS peptides in canine heart disease; leaves open therapeutic potential of rhACE2 modulation.
BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a homologue of angiotensin-converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1-9 and 1-7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty-nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1-12.1) as compared to control (2.2 mU/mg; IQR, 1.8-3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1-7, in dogs with CHF (486.7 pg/mL; IQR, 214.2-1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4-45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1-25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1-9 (preincubation, 10.3 pg/mL; IQR, 4.4-37.2; postincubation, 2431 pg/mL; IQR, 1355-3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6-226.4; postincubation, 2.4 pg/mL; IQR, 0.50-5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.
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Larouche‐Lebel et al. (2019) conducted an observational in Heart disease (n=83). Congestive heart failure vs. Healthy controls was evaluated on Median plasma ACE2 activity (mU/mg) (p=.0003). Dogs with congestive heart failure had significantly higher median plasma ACE2 activity (6.9 vs 2.2 mU/mg; P=0.0003) and beneficial angiotensin peptides compared to healthy controls.
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