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Effect of ramipril on kidney, lung and heart ACE2 in a diabetic mice model
Ander Vergara1, Conxita Jacobs-Cachá2, Mireia Molina-Van den Bosch3
1Nephrology Department. Vall d'Hebrón Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Nephrology Research Group, Vall d'Hebrón Research Institute (VHIR), Vall d'Hebrón Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Background:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19). The main organ affected in this infection is the lung and the virus uses the angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the target cells. In this context, a controversy raised regarding the use of renin-angiotensin system (RAAS) blockers, as these drugs might increase ACE2 expression in some tissues and potentially increase the risk for SARS-CoV-2 infection. This is specially concerning in diabetic patients as diabetes is a risk factor for COVID-19.
Methods:
12-week old diabetic mice (db/db) were treated with ramipril, or vehicle control for 8 weeks. Non-diabetic db/m mice were included as controls. ACE2 expression and activity were studied in lung, kidney and heart of these animals.
Results:
Kidney ACE2 activity was increased in the db/db mice as compared to the db/m (143.2% ± 23% vs 100% ± 22.3%, p = 0.004), whereas ramipril had no significant effect. In the lung, no differences were found in ACE2 when comparing db/db mice to db/m and ramipril also had no significant effect. In the heart, diabetes decreased ACE2 activity (83% ± 16.8%, vs 100% ± 23.1% p = 0.02), and ramipril increased ACE2 significantly (83% ± 16.8% vs 98.2% ± 15%, p = 0.04).
Conclusions:
In a mouse model of type 2 diabetes, ramipril had no significant effect on ACE2 activity in either kidneys or in the lungs. Therefore, it is unlikely that RAAS blockers or at least angiotensin-converting enzyme inhibitors increase the risk of SARS-CoV-2 infection through increasing ACE2.
Insights
Ramipril did not alter angiotensin-converting enzyme 2 (ACE2) activity in the kidneys or lungs of diabetic mice. This suggests that renin-angiotensin system (RAAS) blockers are unlikely to increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Area of Science:
- Biomedical Science
- Pharmacology
- Infectious Disease
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes angiotensin-converting enzyme 2 (ACE2) as a cellular receptor.
- Diabetes mellitus is a significant risk factor for severe COVID-19.
- Concerns exist regarding renin-angiotensin system (RAAS) blockers potentially increasing ACE2 expression and SARS-CoV-2 infection risk.
Purpose of the Study:
- To investigate the effect of ramipril on ACE2 activity in diabetic mice.
- To determine if RAAS inhibition influences ACE2 expression in key organs relevant to SARS-CoV-2 infection.
Main Methods:
- Diabetic mice (db/db) and non-diabetic controls (db/m) were treated with ramipril or vehicle for 8 weeks.
- ACE2 expression and activity were quantified in lung, kidney, and heart tissues.
- Statistical analysis was performed to compare treatment groups.
Main Results:
- Kidney ACE2 activity was elevated in diabetic mice but unaffected by ramipril.
- Lung ACE2 activity showed no significant differences between diabetic and non-diabetic mice, nor was it affected by ramipril.
- Heart ACE2 activity was reduced in diabetic mice, but significantly increased by ramipril treatment.
Conclusions:
- Ramipril does not significantly alter ACE2 activity in the kidneys or lungs of diabetic mice.
- The findings suggest that ACE inhibitors like ramipril are unlikely to increase SARS-CoV-2 infection risk by upregulating ACE2.
- Further research may be warranted to fully elucidate the complex interactions between diabetes, RAAS, and COVID-19.
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