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February 1, 2011Cardiovascular ResearchOpen Access

Enhanced susceptibility to biomechanical stress in ACE2 null mice is prevented by loss of the p47phox NADPH oxidase subunit

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Key result

Loss of the p47phox subunit or Ang 1-7 supplementation in ACE2 knockout mice normalized increased NADPH oxidase activity, superoxide production, and systolic dysfunction following pressure overload.

Why the study?

Does loss of p47phox or Ang 1-7 supplementation prevent enhanced susceptibility to biomechanical stress and heart failure in ACE2 null mice?

Population

Wild-type (Ace2), ACE2 knockout (ACE2KO, Ace2), p47 knockout (p47KO, p47), and ACE2/p47 double KO mice…

Comparison

Loss of p47phox or Ang 1-7 supplementation vs ACE2KO mice without p47phox loss or Ang 1-7…

Design

Preclinical

Authors

SBSreedhar BodigaJZJiu Chang ZhongWWWang Wang

Discussion

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Overview

Should not change clinical practice in heart failure; extends mechanistic evidence for p47phox and Ang 1-7 in ACE2-deficient models.

Key Points

  • This study aims to investigate how ACE2 deficiency affects heart function and the role of the NADPH oxidase system in heart disease.
  • Used aortic constriction model on wild-type, ACE2KO, p47(phox)KO, and double KO mice
  • Measured NADPH oxidase activity, gene expression, and heart function following pressure overload
  • Examined peptide levels and MMP activity to assess myocardial health
  • ACE2KO mice exhibited increased NADPH oxidase activity and superoxide production leading to heart dysfunction
  • Loss of p47(phox) in ACE2KO mice normalized NADPH oxidase activity and improved systolic function
  • Ang 1-7 supplementation reduced NADPH oxidase activity and improved early dilated cardiomyopathy in ACE2KO mice

Structured PICO

Does loss of p47phox or Ang 1-7 supplementation prevent enhanced susceptibility to biomechanical stress and heart failure in ACE2 null mice?

P
Population
Wild-type (Ace2(+/y)), ACE2 knockout (ACE2KO, Ace2(-/y)), p47(phox) knockout (p47(phox)KO, p47(phox-)(/-)), and ACE2/p47(phox) double KO mice subjected to pressure overload via aortic constriction model
I
Intervention
Loss of p47phox (double KO) or Ang 1-7 supplementation
C
Comparator
ACE2KO mice without p47phox loss or Ang 1-7 supplementation, and wild-type mice
O
Outcome
Changes in peptide levels, NADPH oxidase activity, gene expression, matrix metalloproteinases (MMP) activity, pathological signalling, and heart functionsurrogate

In ACE2-deficient mice, biomechanical stress activates the myocardial NADPH oxidase system via the p47phox subunit, leading to adverse remodeling that can be prevented by p47phox deletion or Ang 1-7 supplementation.

Cite This Study

Bodiga et al. (2011) studied Pressure overload-induced heart failure. Loss of p47phox (double knockout) or Ang 1-7 supplementation vs. ACE2 knockout mice and wild-type mice was evaluated on Changes in peptide levels, NADPH oxidase activity, gene expression, MMP activity, pathological signalling, and heart function. Loss of the p47phox subunit or Ang 1-7 supplementation in ACE2 knockout mice normalized increased NADPH oxidase activity, superoxide production, and systolic dysfunction following pressure overload.

synapsesocial.com/papers/6a0f1abea7a2fed64abdb72dhttps://doi.org/10.1093/cvr/cvr036
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Also Consider

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

  1. 1Angiotensin II-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice2007 · 249 citations
  2. 2Deletion of Angiotensin-Converting Enzyme 2 Accelerates Pressure Overload-Induced Cardiac Dysfunction by Increasing Local Angiotensin II2006 · 324 citations
  3. 3Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis2008 · 309 citations
  4. 4Regulation of ACE2 in cardiac myocytes and fibroblasts2008 · 231 citations
  5. 5Activation of NADPH Oxidase During Progression of Cardiac Hypertrophy to Failure2002 · 518 citations