Evidence map›Paper›PMID 30773786›Full record

ArticleAging cell2019

The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation.

Alejandra Romero, Álvaro San Hipólito-Luengo, Laura A Villalobos, Susana Vallejo, Inés Valencia, Patrycja Michalska, Natalia Pajuelo-Lozano, Isabel Sánchez-Pérez, Rafael León, José Luis Bartha and 5 more

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

71 citing papers in PubMed, 121 citations in OpenAlex.

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11 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

15 authors at 7 institutions in 2 countries.

Alejandra RomeroDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Álvaro San Hipólito-LuengoDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Laura A VillalobosDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Susana VallejoDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Inés ValenciaDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Patrycja MichalskaDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Natalia Pajuelo-LozanoDepartment of Biochemistry, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Isabel Sánchez-PérezDepartment of Biochemistry, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Rafael LeónInstituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain.
José Luis BarthaInstituto de Investigaciones Sanitarias IdiPAZ, Madrid, Spain.
María Jesús SanzDepartment of Pharmacology, Universidad de Valencia, Valencia, Spain.
Jorge D ErusalimskySchool of Sport and Health Sciences, Cardiff Metropolitan University, Cardiff, UK.
Carlos F Sánchez-FerrerDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Tania RomachoDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Concepción PeiróDepartment of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
Universidad Autónoma de Madrid · ESHospital La Paz Institute for Health Research · ESCardiff Metropolitan University · GBCentre for Biomedical Network Research on Rare Diseases · ESHospital Universitario de La Princesa · ESInstituto de Investigaciones Biomédicas Sols-Morreale · ESUniversitat de València · ES

Funding

Fundación La Caixa CaixaImpulse CI17/00048IS Carlos III PI17/01401IS Carlos III PI17/01700Plan Nacional I+D+i SAF2017-84776-RPlan Nacional I+D+i SAF2017-89714-R
6 · The paper itself

Abstract

Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin-angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers. By activating the G protein-coupled receptor Mas, Ang-(1-7) inhibited the pro-senescence action of Ang II, but also of a non-RAS stressor such as the cytokine IL-1β. Moreover, Ang-(1-7) enhanced endothelial klotho levels, while klotho silencing resulted in the loss of the anti-senescence action of the heptapeptide. Indeed, both Ang-(1-7) and recombinant klotho activated the cytoprotective Nrf2/heme oxygenase-1 (HO-1) pathway. The HO-1 inhibitor tin protoporphyrin IX prevented the anti-senescence action evoked by Ang-(1-7) or recombinant klotho. Overall, the present study identifies Ang-(1-7) as an anti-senescence peptide displaying its protective action beyond the RAS by consecutively activating klotho and Nrf2/HO-1. Ang-(1-7) mimetic drugs may thus prove useful to prevent endothelial cell senescence and its related vascular complications.

Indexed as

Angiotensin ICells, CulturedCellular SenescenceGlucuronidaseHumansHuman Umbilical Vein Endothelial CellsKlotho ProteinsNF-E2-Related Factor 2Peptide FragmentsReceptors, G-Protein-CoupledAngiotensin Iangiotensin I (1-7)GlucuronidaseKlotho ProteinsNFE2L2 protein, humanNF-E2-Related Factor 2Peptide FragmentsReceptors, G-Protein-Coupledangiotensin-(1-7)endothelial senescenceheme oxygenase-1klothonuclear factor (erythroid-derived 2)-like 2vascular aging

Identifiers

PMID30773786
PMCPMC6516147
OpenAlexW2915311716

What OpenQuestion holds

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Registered trials

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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.