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Published on: May 26, 2022
Angiotensin-(1-7) administration benefits cardiac, renal and progenitor cell function in db/db mice
A M Papinska1, N M Mordwinkin1, C J Meeks1
1School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
Background And Purpose:
Diabetic patients are at an increased risk of cardiovascular disease, in part due to inflammation and oxidative stress. These two pathological mechanisms also affect other organs and cells including the kidneys and progenitor cells. Angiotensin-(1-7) [Ang-(1-7)] has previously been shown to counterbalance pathological effects of angiotensin II, including inflammation and oxidative stress. The aim of this study was to investigate the effects of short-term (2 weeks) Ang-(1-7) treatment on cardiovascular and renal function in a mouse model of type 2 diabetes (db/db).
Experimental Approach:
Eight- to nine-week-old db/db mice were administered either vehicle, Ang-(1-7) alone, or Ang-(1-7) combined with an inhibitor (losartan, PD123319, A-779, L-NAME or icatibant) daily for 14 days.
Key Results:
An improvement in physiological heart function was observed in Ang-(1-7)-treated mice. Ang-(1-7) also reduced cardiomyocyte hypertrophy, fibrosis and inflammatory cell infiltration of the heart tissue and increased blood vessel number. These changes were blocked by antagonists of the MAS1, AT2 and bradykinin receptors and inhibition of NO formation. Treatment with Ang-(1-7) reduced glomerular damage and oxidative stress in kidney tissue. Bone marrow and circulating endothelial progenitors, as well as bone marrow mesenchymal stem cells, were increased in mice treated with Ang-(1-7).
Conclusions And Implications:
Short-term Ang-(1-7) treatment of young db/db mice improved heart function and reduced kidney damage. Treatment also improved bone marrow and circulating levels of endothelial and mesenchymal stem cells. All of this may contribute to improved cardiovascular and renal function.
Insights
Short-term treatment with Angiotensin-(1-7) [Ang-(1-7)] improved heart function and reduced kidney damage in diabetic mice. This peptide therapy also enhanced stem cell levels, potentially improving cardiovascular and renal health.
Area of Science:
- Cardiovascular Science
- Nephrology
- Endocrinology
Background:
- Diabetic patients face elevated cardiovascular disease risk due to inflammation and oxidative stress.
- These factors also negatively impact kidney and progenitor cells.
- Angiotensin-(1-7) [Ang-(1-7)] counterbalances angiotensin II's detrimental effects.
Purpose of the Study:
- Investigate short-term Ang-(1-7) effects on cardiovascular and renal function.
- Assess Ang-(1-7) impact in a type 2 diabetes mouse model (db/db).
Main Methods:
- db/db mice received vehicle or Ang-(1-7) for 14 days.
- Ang-(1-7) was administered alone or with receptor inhibitors (losartan, PD123319, A-779, icatibant) or L-NAME.
- Physiological and tissue analyses were performed.
Main Results:
- Ang-(1-7) improved heart function, reduced cardiac hypertrophy, fibrosis, and inflammation, and increased vascularity.
- Kidney damage and oxidative stress were reduced by Ang-(1-7).
- Bone marrow and circulating endothelial progenitors and mesenchymal stem cells increased with Ang-(1-7) treatment.
Conclusions:
- Short-term Ang-(1-7) therapy benefits heart function and kidney health in young diabetic mice.
- The treatment boosts endothelial and mesenchymal stem cell populations.
- These improvements may enhance overall cardiovascular and renal function.
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