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Updated: Apr 16, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Endogenous activated angiotensin-(1-7) plays a protective effect against atherosclerotic plaques unstability in high
Jianmin Yang1, Xiaoyan Yang1, Xiao Meng1
1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, PR China.
Background And Objective:
We recently found that exogenous angiotensin-(1-7) [Ang-(1-7)] inhibits Angiotensin II (Ang-II)-induced atherosclerotic lesion formation and enhances plaque stability. Our objective was to evaluate the role of endogenous activated Ang-(1-7) during atherosclerosis.
Methods And Results:
In mice, the effects of endogenous Ang-(1-7) on atherogenesis in early stage and plaque stability in late stage were observed in ApoE knockout (ApoE-/-) mice fed with a high fat diet. Blockage of endogenous Ang-(1-7) with A779, an Ang-(1-7) antagonist, did not increase early plaque lesion formation, however, it remarkably enhanced contents of lipids and macrophages and decreased contents of vascular smooth muscle cells (VSMCs) and collagens in late lesions. The expressions of proinflammatory cytokines, and the expressions and activities of matrix metalloproteinases were significantly elevated in A779-treated group than those in vehicle-treated group in late lesions. Exogenous Ang-(1-7) treatment attenuated early atherosclerotic plaque formation and enhanced late plaques stability in this model. The contents of Ang-II and Ang-(1-7) and activity of ACE2 in late atherosclerotic plaques were higher than those of early atherosclerotic lesions.
Conclusion:
Endogenous activated Ang-(1-7) enhanced late atherosclerotic plaques stability but did not affect early atherosclerotic plaque formation. Therapies to elevate endogenous Ang-(1-7) may be a potentially effective approach to attenuate atherosclerotic plaques vulnerability.
Insights
Endogenous angiotensin-(1-7) [Ang-(1-7)] stabilizes late atherosclerotic plaques but does not impact early lesion formation. Therapies boosting Ang-(1-7) may reduce plaque vulnerability.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Vascular Biology
Background:
- Exogenous angiotensin-(1-7) [Ang-(1-7)] inhibits Angiotensin II (Ang-II)-induced atherosclerosis and improves plaque stability.
- The role of endogenous Ang-(1-7) in atherosclerosis remains to be fully elucidated.
Purpose of the Study:
- To evaluate the role of endogenous activated Ang-(1-7) in the development and progression of atherosclerosis.
Main Methods:
- ApoE knockout (ApoE-/-) mice on a high-fat diet were used to study atherogenesis.
- Endogenous Ang-(1-7) was blocked using the antagonist A779.
- Lesion formation, plaque composition (lipids, macrophages, VSMCs, collagen), and inflammatory markers were analyzed.
Main Results:
- Blocking endogenous Ang-(1-7) did not affect early plaque formation but worsened late plaque stability.
- A779 treatment increased lipids and macrophages, while decreasing VSMCs and collagen in late lesions.
- Proinflammatory cytokines and matrix metalloproteinases were elevated in the A779-treated group.
- Exogenous Ang-(1-7) attenuated early plaque formation and enhanced late plaque stability.
- Ang-II, Ang-(1-7), and ACE2 levels were higher in late vs. early lesions.
Conclusions:
- Endogenous Ang-(1-7) enhances atherosclerotic plaque stability in later stages.
- Endogenous Ang-(1-7) does not influence early atherosclerotic plaque formation.
- Therapeutic strategies aimed at increasing endogenous Ang-(1-7) show promise for treating atherosclerotic plaque vulnerability.
