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June 5, 2012PLoS ONEOpen Access

ACE2 deficiency worsens Angiotensin II-mediated aortic inflammation and peroxynitrite production by augmenting profilin-1 expression and activating Akt-ERK-eNOS signaling pathways.

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Why the study?

Does ACE2 deficiency exacerbate Angiotensin II-mediated aortic inflammation and peroxynitrite production in a mouse model?

Population

10-week-old male wildtype (WT, Ace2+/y) and ACE2 knockout (ACE2KO, Ace2-/y) mice

Comparison

Angiotensin II via mini-osmotic pumps for 2… vs Saline infusion via mini-osmotic pumps

Design

Preclinical, randomized to either Ang II or saline infusion

Follow-up

2 weeks

Key result

ACE2 deficiency worsens Angiotensin II-mediated aortic inflammation and peroxynitrite production by augmenting profilin-1 expression and activating Akt-ERK-eNOS signaling pathways.

Authors

HJHaiyan JinBSBei SongGOGavin Y. Oudit

Discussion

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Member takes

Overview

ACE2 augmentation merits exploration in vascular inflammation models; leaves open translation to human aortic disease.

Structured PICO

Does ACE2 deficiency exacerbate Angiotensin II-mediated aortic inflammation and peroxynitrite production in a mouse model?

P
Population
10-week-old male wild-type and ACE2 knockout mice subjected to Angiotensin II infusion for 2 weeks to evaluate vascular inflammation and oxidative stress.
E
Exposure
Angiotensin II (1.5 mg/kg/day) via mini-osmotic pumps for 2 weeks, with or without irbesartan (50 mg/kg/day) in drinking water
C
Comparator
Saline infusion via mini-osmotic pumps
O
Outcome
Aortic inflammation (mRNA expressions of MCP-1, IL-1b, IL-6) and peroxynitrite production (nitrotyrosine staining and protein levels)surrogate

Main Result

p-value: p=<0.05

ACE2 deficiency worsens Angiotensin II-mediated vascular inflammation and oxidative stress, suggesting enhancing ACE2 action may be a potential therapeutic approach for vascular diseases.

Limitations

  • The exact role and mechanism of profilin-1 in vascular inflammation and peroxynitrite production require further investigation.

Cite This Study

Jin et al. (2012) studied Angiotensin II-mediated vascular inflammation and oxidative stress. ACE2 deficiency vs. Wild-type mice was evaluated on Aortic inflammation and peroxynitrite production (p=<0.05). ACE2 deficiency worsens Angiotensin II-mediated aortic inflammation and peroxynitrite production by augmenting profilin-1 expression and activating Akt-ERK-eNOS signaling pathways.

synapsesocial.com/papers/6a98bb6e52d74751e81fea39https://doi.org/10.1371/journal.pone.0038502
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Also Consider

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

  1. 1Deletion of angiotensin-converting enzyme 2 promotes the development of atherosclerosis and arterial neointima formation2013 · 72 citations
  2. 2Prevention of Angiotensin II–Mediated Renal Oxidative Stress, Inflammation, and Fibrosis by Angiotensin-Converting Enzyme 22010 · 231 citations
  3. 3Angiotensin-Converting Enzyme 2 Is a Critical Determinant of Angiotensin II–Induced Loss of Vascular Smooth Muscle Cells and Adverse Vascular Remodeling2014 · 97 citations
  4. 4Enhanced Angiotensin II-Induced Cardiac and Aortic Remodeling in ACE2 Knockout Mice2012 · 57 citations
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