Evidence map›Paper›PMID 35113975›Full record

ArticlePloS one2022

Reduced blood pressure in sickle cell disease is associated with decreased angiotensin converting enzyme (ACE) activity and is not modulated by ACE inhibition.

Pamela L Brito, Alisson F Dos Santos, Hanan Chweih, Maria E Favero, Erica M F Gotardo, Juliete A F Silva, Flavia C Leonardo, Carla F Franco-Penteado, Mariana G de Oliveira, Wilson A Ferreira and 8 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

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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

18 authors at 2 institutions in 1 country.

Pamela L BritoHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Alisson F Dos SantosCentro de Hematologia e Hemoterapia do Paraná, Curitiba, Paraná, Brazil.
Hanan ChweihHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Maria E FaveroUniversity Hospital, State University of Londrina, Londrina, Brazil.
Erica M F GotardoHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Juliete A F SilvaHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.ORCID 0000-0002-4543-5169
Flavia C LeonardoHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Carla F Franco-PenteadoHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Mariana G de OliveiraDepartment of Pharmacology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Wilson A FerreiraHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Bruna C ZaidanDepartment of Pathology, School of Medical Sciences, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Athanase BillisDepartment of Pathology, School of Medical Sciences, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Giorgio BaldanziCentro de Hematologia e Hemoterapia do Paraná, Curitiba, Paraná, Brazil.
Denise A MashimaUniversity Hospital, State University of Londrina, Londrina, Brazil.
Edson AntunesDepartment of Pharmacology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Sara T Olalla SaadHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Fernando F CostaHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Nicola ConranHematology and Transfusion Center, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.ORCID 0000-0001-5726-7919
Universidade Estadual de Campinas (UNICAMP) · BRUniversidade Estadual de Londrina · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSickle cell disease (SCD) incurs vaso-occlusive episodes and organ damage, including nephropathy. Despite displaying characteristics of vascular dysfunction, SCD patients tend to present relatively lower systemic blood pressure (BP), via an unknown mechanism. We investigated associations between BP and renin-angiotensin-system (RAS) components in SCD and determined whether an inhibitor of angiotensin converting enzyme (ACE; often used to slow SCD glomerulopathy) further modulates BP and RAS components in a murine model of SCD.

methodsBP was compared in human subjects and mice with/without SCD. Plasma angiotensin II, ACE and renin were measured by immunoassay. BP was reevaluated after treating mice with enalapril (25 mg/kg, 5x/week) for 5 weeks; plasma and organs were stored for angiotensin II and ACE activity measurement, and quantitative real-time PCR.

resultsDiastolic BP and systolic BP were significantly lower in patients and mice with SCD, respectively, compared to controls. Reduced BP was associated with increased plasma renin and markers of kidney damage (mice) in SCD, as well as significantly decreased plasma ACE concentrations and ACE enzyme activity. As expected, enalapril administration lowered BP, plasma angiotensin II and organ ACE activity in control mice. In contrast, enalapril did not further reduce BP or organ ACE activity in SCD mice; however, plasma angiotensin II and renin levels were found to be significantly higher in enalapril-treated SCD mice than those of treated control mice.

conclusionRelative hypotension was confirmed in a murine model of SCD, in association with decreased ACE concentrations in both human and murine disease. Given that ACE inhibition has an accepted role in decreasing BP, further studies should investigate mechanisms by which ACE depletion, via both Ang II-dependent and alternative pathways, could contribute to reduce BP in SCD and understand how ACE inhibition confers Ang II-independent benefits on kidney function in SCD.

Indexed as

AdolescentAdultAnemia, Sickle CellAngiotensin-Converting Enzyme InhibitorsAngiotensin IIAnimalsBlood PressureDiastoleDisease Models, AnimalFemaleHumansHydroxyureaMaleMiceMice, Inbred C57BLMiddle AgedACE protein, humanAngiotensin-Converting Enzyme InhibitorsAngiotensin IIHydroxyureaPeptidyl-Dipeptidase ARenin

Identifiers

PMID35113975
PMCPMC8812860
OpenAlexW4210358202

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.