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Published on: June 7, 2016
Fecal ACE and ACE2 Activities Reflect Intestinal Shedding and Microbiota Modulation of Renin-Angiotensin System
Mariana Ferreira-Duarte1,2, Clara Quintas1,3, Joana Bom4
1Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy of the University of Porto (FFUP), 4050-313 Porto, Portugal.
Fecal angiotensin-converting enzyme (ACE) and ACE2 activity originate from both intestinal shedding and gut microbes. The gut environment modulates this luminal renin-angiotensin-aldosterone system activity.
Area of Science:
- Gastroenterology and Endocrinology
- Enzymology
- Microbiome Research
Background:
- Angiotensin-converting enzymes (ACE and ACE2) are crucial for the renin-angiotensin-aldosterone system (RAAS).
- These enzymes are found in the gastrointestinal tract and may interact with gut microbiota.
- Their presence and activity in fecal matter suggest a role in luminal RAAS regulation.
Purpose of the Study:
- To investigate the sources of fecal ACE and ACE2 activity.
- To differentiate between intestinal shedding and microbiota contributions.
- To understand the influence of the gut environment on luminal RAAS.
Main Methods:
- Analysis of fecal pellets from germ-free, ACE knockout (KO), and ACE2 knockout (KO) mice.
- Fluorimetric enzyme activity assays using specific substrates for ACE and ACE2.
- Enzyme inhibition assays using captopril and MLN-4760.
Main Results:
- Germ-free mice exhibited higher fecal ACE and ACE2 activity.
- ACE2 knockout mice lacked fecal ACE2 activity, while ACE activity was unchanged.
- ACE knockout mice showed reduced fecal ACE activity, but ACE2 activity remained unaffected.
- Specific ACE domain knockouts and captopril inhibition provided further insights into ACE activity origins.
Conclusions:
- Fecal ACE and ACE2 activity are derived from a combination of intestinal shedding and gut microbiota.
- The gut environment plays a significant role in modulating luminal RAAS activity.
- These findings highlight the interplay between host enzymes and the microbiome in digestive health.
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