Evidence map›Paper›PMID 29691064›Full record

ArticleKidney international2018

Novel ACE2-Fc chimeric fusion provides long-lasting hypertension control and organ protection in mouse models of systemic renin angiotensin system activation.

Pan Liu, Jan Wysocki, Tomokazu Souma, Minghao Ye, Veronica Ramirez, Bisheng Zhou, Lisa D Wilsbacher, Susan E Quaggin, Daniel Batlle, Jing Jin

Open access · bronzeAbstract read
In one paragraph

Article in Kidney international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 2 pooled it
11.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.

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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Pan LiuDivision of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Jan WysockiDivision of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Tomokazu SoumaDivision of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Minghao YeDivision of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Veronica RamirezDivision of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Bisheng ZhouFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Lisa D WilsbacherFeinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Susan E QuagginDivision of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Daniel BatlleDivision of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Jing JinDivision of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address: jing.jin@northwestern.edu.
Northwestern University · US

Funding

Urinary Renin Angiotensin System in DiabetesR01DK104785 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BATLLE, DANIEL · 2015 to 2017
$939k
NIDDK NIH HHS R01 DK104785
6 · The paper itself

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that potently degrades angiotensin II to angiotensin 1-7. Previous studies showed that injection of the enzymatic ectodomain of recombinant ACE2 (rACE2) markedly increases circulatory levels of ACE2 activity, and effectively lowered blood pressure in angiotensin II-induced hypertension. However, due to the short plasma half-life of rACE2, its therapeutic potential for chronic use is limited. To circumvent this, we generated a chimeric fusion of rACE2 and the immunoglobulin fragment Fc segment to increase its plasma stability. This rACE2-Fc fusion protein retained full peptidase activity and exhibited greatly extended plasma half-life in mice, from less than two hours of the original rACE2, to over a week. A single 2.5 mg/kg injection of rACE2-Fc increased the overall angiotensin II-conversion activities in blood by up to 100-fold and enhanced blood pressure recovery from acute angiotensin II induced hypertension seven days after administration. To assess rACE2-Fc given weekly on cardiac protection, we performed studies in mice continuously infused with angiotensin II for 28 days and in a Renin transgenic mouse model of hypertension. The angiotensin II infused mice achieved sustained blood pressure control and reduced cardiac hypertrophy and fibrosis. In chronic hypertensive transgenic mice, weekly injections of rACE2-Fc effectively lowered plasma angiotensin II and blood pressure. Additionally, rACE2-Fc ameliorated albuminuria, and reduced kidney and cardiac fibrosis. Thus, our chimeric fusion strategy for rACE2-Fc is suitable for future development of new renin angiotensin system-based inhibition therapies.

Indexed as

Angiotensin-Converting Enzyme 2Angiotensin IIAnimalsCell LineDisease Models, AnimalFemaleHalf-LifeHumansHypertensionImmunoglobulin Fc FragmentsMiceMice, Inbred BALB CPeptidyl-Dipeptidase ARecombinant Fusion ProteinsReninRenin-Angiotensin SystemACE2 protein, humanAce2 protein, mouseAngiotensin-Converting Enzyme 2Angiotensin IIImmunoglobulin Fc FragmentsPeptidyl-Dipeptidase ARecombinant Fusion ProteinsReninangiotensin 1–7angiotensin-converting enzyme 2angiotensin IIFc fusionhypertensionproteinuriarenin-angiotensin system

Identifiers

PMID29691064
PMCPMC13662898
OpenAlexW2802659015

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.