Article Impact Level: HIGH Data Quality: STRONG Summary of Hypertension Research, 48(4), 1477–1490. https://doi.org/10.1038/s41440-025-02109-y Dr. Smruti K. Nair et al.
Points
- This study investigates the potential benefits of adding oral ACE2 to hypertension treatment, specifically in dogs with myxomatous mitral valve disease (MMVD), showing no adverse events with the bioencapsulated ACE2.
- The addition of ACE2 significantly increased serum ACE2 activity by 670-755%, especially when combined with ARB Telmisartan, while ACEIs like Enalapril inhibited ACE2 activity by over 90%.
- ACEIs decreased angiotensin II (Ang-II) levels by 11-20 times, while ARBs increased Ang-II levels by 11-20 times and enhanced Ang1-7 levels by 160-260%, affecting blood pressure regulation differently.
- ARB treatment provided better regulation of systolic blood pressure than ACEIs; despite higher levels of Ang-II, ACE2 supplementation reduced cardiovascular risk factors, offering potential therapeutic benefits.
- The study suggests that ACE2 supplementation combined with ACEIs or ARBs could help manage elevated blood pressure and cardiovascular conditions, and it recommends further research and clinical trials for human applications.
Summary
This study explores the potential benefits of adding oral ACE2 to the treatment regimen for hypertension, specifically in patients with myxomatous mitral valve disease (MMVD). The researchers focused on pet dogs with elevated systolic blood pressure, who were already being treated with angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs). In this model, the addition of ACE2, bioencapsulated in plant cells, was well tolerated with no adverse events. The results revealed that ACE2 significantly increased serum ACE2 activity by 670-755%, mainly when used alongside ARB (Telmisartan), compared to ACEI (Enalapril) treatment. The study found that ACEIs inhibited ACE2 activity by over 90%, while ARBs showed less inhibition.
The analysis also showed how ACEIs and ARBs influenced the renin-angiotensin system (RAS). ACEI treatment decreased the angiotensin II (Ang-II) pool by 11-20 times, while ARB treatment increased the Ang-II pool by 11-20 times and enhanced Ang1-7 levels by 160-260%. These changes in the RAS pathway had distinct effects on blood pressure regulation. The ARB group demonstrated better systolic blood pressure regulation than ACEIs despite very high levels of Ang-II. Additionally, ACE2 supplementation in these models reduced key cardiovascular risk factors, offering potential therapeutic insights for human clinical applications.
In conclusion, this study demonstrates that ACE2 supplementation, combined with existing therapies like ACEIs or ARBs, could help mitigate the detrimental effects of elevated blood pressure in patients, especially those with underlying heart disease. The findings suggest that further research, including studies with lisinopril (which has a lower inhibitory effect on ACE2) and clinical trials in humans, could lead to novel, affordable biological therapies for hypertension and related cardiovascular conditions. These results have important implications for future treatment strategies in managing cardiovascular diseases.
Link to the article: https://www.nature.com/articles/s41440-025-02109-y
References Nair, S. K., Hersh, E. V., Margulies, K. B., & Daniell, H. (2025). Clinical studies in Myxomatous Mitral Valve Disease dogs: Most prescribed ACEI inhibits ACE2 enzyme activity and ARB increases AngII pool in plasma. Hypertension Research, 48(4), 1477–1490. https://doi.org/10.1038/s41440-025-02109-y
