Interaction of diabetes and ACE2 in the pathogenesis of cardiovascular disease in experimental diabetes
Abstract
Local and systemic AngII (angiotensin II) levels are regulated by ACE2 (angiotensin-converting enzyme 2), which is reduced in diabetic tissues. In the present study, we examine the effect of ACE2 deficiency on the early cardiac and vascular changes associated with experimental diabetes. Streptozotocin diabetes was induced in male C57BL6 mice and Ace2-KO (knockout) mice, and markers of RAS (renin-angiotensin system) activity, cardiac function and injury were assessed after 10 weeks. In a second protocol, diabetes was induced in male ApoE (apolipoprotein E)-KO mice and ApoE/Ace2-double-KO mice, and plaque accumulation and markers of atherogenesis assessed after 20 weeks. The induction of diabetes in wild-type mice led to reduced ACE2 expression and activity in the heart, elevated circulating AngII levels and reduced cardiac Ang-(1-7) [angiotensin-(1-7)] levels. This was associated structurally with thinning of the LV (left ventricular) wall and mild ventricular dilatation, and histologically with increased cardiomyocyte apoptosis on TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) staining and compensatory hypertrophy denoted by an increased cardiomyocyte cross-sectional area. By contrast Ace2-KO mice failed to increase circulating AngII concentration, experienced a paradoxical fall in cardiac AngII levels and no change in Ang-(1-7) following the onset of diabetes. At the same time the major phenotypic differences between Ace2-deficient and Ace2-re…
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Ang II binds the ATR1 receptor leading to release of TNFα and IL-6, which is associated with hypertension, diabetes, and heart disease-major comorbidities in severe COVID-19.
“Ang II binds the ATR1 (Ang II receptor 1) receptor leading to release of TNF α and IL-6, 55 which is associated with hypertension, diabetes, and heart disease 52,56,57 -major comorbidities in severe COVID-19.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [56]
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- Authors
- Tikellis, C., Pickering, R., Tsorotes, D., Du, X.-J., Kiriazis, H., Nguyen-Huu, T.-P., Head, G. A., Cooper, M. E., & Thomas, M. C.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Central, Melbourne 8008, Australia
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2012-07-03
- Volume
- 123
- Issue
- 8
- Pages
- 519-529
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W1973263005
- Cited by
- 57
- References
- 41
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 13 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 6 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 1
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- ACE2, diabetes mellitus, angiotensin II, renin-angiotensin system, angiotensin-(1-7), atherosclerosis, cardiomyocyte apoptosis, cardiac hypertrophy, left ventricular wall thinning, blood pressure, ApoE-deficient mice, streptozotocin-induced diabetes, cardiovascular disease, adhesion molecules
- MeSH terms
- Angiotensin-Converting Enzyme 2, Angiotensin II, Animals, Aortic Diseases, Blood Pressure, Cardiovascular Diseases, Diabetes Mellitus, Experimental, Diabetic Angiopathies, Peptidyl-Dipeptidase A, Male, Mice, Inbred C57BL, Myocardium, Telemetry, Biomarkers, Apoptosis, Mice, Knockout, Inflammation Mediators, Mice, Plaque, Atherosclerotic
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