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October 10, 2014Arteriosclerosis Thrombosis and Vascular BiologyOpen Access

Administration of diminazene aceturate significantly decreased aortic lumen diameters and aortic external diameters of AngII-infused mice, resulting in a marked reduction in AAA incidence from 73% to 29%.

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Why the study?

Does ACE2 activation by diminazene aceturate reduce the formation and severity of AngII-induced abdominal aortic aneurysms in hypercholesterolemic mice?

Population

Hypercholesterolemic male mice (Ldlr and Ace2) infused with Angiotensin II to induce abdominal aortic…

Comparison

ACE2 activation by administration of diminazene… vs Control mice.

Design

Preclinical

Authors

STSean E. ThatcherXZXuan ZhangDHDeborah A. Howatt

Discussion

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Overview

ACE2 activation merits further preclinical testing for AAA; leaves open translation to human prevention or therapy.

Structured PICO

Does ACE2 activation by diminazene aceturate reduce the formation and severity of AngII-induced abdominal aortic aneurysms in hypercholesterolemic mice?

P
Population
Hypercholesterolemic male mice (Ldlr(-/-) and Ace2(-/y)) infused with Angiotensin II to induce abdominal aortic aneurysms, and human AAA samples.
I
Intervention
ACE2 activation by administration of diminazene aceturate (30 mg/kg per day) or ACE2 deficiency (whole-body or bone marrow-derived).
C
Comparator
Control mice (wild-type or not receiving diminazene aceturate).
O
Outcome
Aortic lumen diameters, external diameters of suprarenal aortas, and AAA incidence.surrogate

ACE2 activation with diminazene aceturate reduces the incidence and severity of Angiotensin II-induced abdominal aortic aneurysms in hypercholesterolemic mice, suggesting a potential therapeutic target.

Cite This Study

Thatcher et al. (2014) studied this question.

synapsesocial.com/papers/6a6fb6516ceb2bbd16dfb796https://doi.org/10.1161/atvbaha.114.304613
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Angiotensin-Converting Enzyme 2 Deficiency in Whole Body or Bone Marrow–Derived Cells Increases Atherosclerosis in Low-Density Lipoprotein Receptor <sup>−/−</sup> Mice2011 · 80 citations
  2. 2Deletion of angiotensin-converting enzyme 2 promotes the development of atherosclerosis and arterial neointima formation2013 · 72 citations
  3. 3Angiotensin-Converting Enzyme 2 Suppresses Pathological Hypertrophy, Myocardial Fibrosis, and Cardiac Dysfunction2010 · 461 citations
  4. 4ACE2 Deficiency Enhances Angiotensin II-Mediated Aortic Profilin-1 Expression, Inflammation and Peroxynitrite Production2012 · 84 citations
  5. 5Involvement of Vascular Angiotensin II-Forming Enzymes in the Progression of Aortic Abdominal Aneurysms in Angiotensin II- Infused ApoE-Deficient Mice2009 · 35 citations