Evidence map›Paper›PMID 36614132›Full record

ArticleInternational journal of molecular sciences2022

Effects of Physiological and Pathological Urea Concentrations on Human Microvascular Endothelial Cells.

Graziano Colombo, Alessandra Altomare, Emanuela Astori, Lucia Landoni, Maria Lisa Garavaglia, Ranieri Rossi, Daniela Giustarini, Maria Chiara Lionetti, Nicoletta Gagliano, Aldo Milzani and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Urinary exosomes as promising biomarkers for early kidney disease detection.American journal of clinical and experimental urology · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. Article
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

11 authors at 2 institutions in 1 country.

Graziano ColomboDepartment of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, 20133 Milan, Italy.
Alessandra AltomareDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0002-9906-6098
Emanuela AstoriDepartment of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, 20133 Milan, Italy.
Lucia LandoniDepartment of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, 20133 Milan, Italy.
Maria Lisa GaravagliaDepartment of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0002-4118-1659
Ranieri RossiDepartment of Biotechnology, Chemistry and Pharmacy (Department of Excellence 2018-2022), University of Siena, 53100 Siena, Italy.
Daniela GiustariniDepartment of Biotechnology, Chemistry and Pharmacy (Department of Excellence 2018-2022), University of Siena, 53100 Siena, Italy.ORCID 0000-0003-4929-5316
Maria Chiara LionettiDepartment of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, 20133 Milan, Italy.
Nicoletta GaglianoDepartment of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0002-3393-3144
Aldo MilzaniDepartment of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, 20133 Milan, Italy.
Isabella Dalle-DonneDepartment of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0001-7098-6213
University of Milan · ITUniversity of Siena · IT

Funding

University of Milan B Piano di Sostegno alla Ricerca 2018-Linea 2
6 · The paper itself

Abstract

Urea is the uremic toxin accumulating with the highest concentration in the plasma of chronic kidney disease (CKD) patients, not being completely cleared by dialysis. Urea accumulation is reported to exert direct and indirect side effects on the gastrointestinal tract, kidneys, adipocytes, and cardiovascular system (CVS), although its pathogenicity is still questioned since studies evaluating its side effects lack homogeneity. Here, we investigated the effects of physiological and pathological urea concentrations on a human endothelial cell line from the microcirculation (Human Microvascular Endothelial Cells-1, HMEC-1). Urea (5 g/L) caused a reduction in the proliferation rate after 72 h of exposure and appeared to be a potential endothelial-to-mesenchymal transition (EndMT) stimulus. Moreover, urea induced actin filament rearrangement, a significant increase in matrix metalloproteinases 2 (MMP-2) expression in the medium, and a significant up- or down-regulation of other EndMT biomarkers (keratin, fibrillin-2, and collagen IV), as highlighted by differential proteomic analysis. Among proteins whose expression was found to be significantly dysregulated following exposure of HMEC-1 to urea, dimethylarginine dimethylaminohydrolase (DDAH) and vasorin turned out to be down-regulated. Both proteins have been directly linked to cardiovascular diseases (CVD) by in vitro and in vivo studies. Future experiments will be needed to deepen their role and investigate the signaling pathways in which they are involved to clarify the possible link between CKD and CVD.

Indexed as

Cardiovascular DiseasesRenal Insufficiency, ChronicEndothelial CellsHumansProteinsProteomicsRenal DialysisUreaProteinsUreaCKDCVDdifferential proteomicsEndMTHMEC-1ureavasorin

Identifiers

PMID36614132
PMCPMC9821335
OpenAlexW4313392014

What OpenQuestion holds

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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 OpenQuestion graph.