Evidence map›Paper›PMID 26861446›Full record

ArticleCardiovascular diabetology2016

Metformin improves the angiogenic potential of human CD34⁺ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction.

Sherin Bakhashab, Fahad W Ahmed, Hans-Juergen Schulten, Ayat Bashir, Sajjad Karim, Abdulrahman L Al-Malki, Mamdooh A Gari, Adel M Abuzenadah, Adeel G Chaudhary, Mohammed H Alqahtani and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
3.6field-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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

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  12. Metformin pre-conditioning enhances the angiogenic ability of the secretome of dental pulp stem cells.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2021
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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

13 authors at 3 institutions in 2 countries.

Sherin BakhashabInstitute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. sbakhashab@kau.edu.sa.
Fahad W AhmedInstitute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. fahad.ahmed@newcastle.ac.uk.
Hans-Juergen SchultenCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. hschulten@kau.edu.sa.
Ayat BashirInstitute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. ayatbashir@yahoo.co.uk.
Sajjad KarimCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. skarim@kau.edu.sa.
Abdulrahman L Al-MalkiBiochemistry Department, King Abdulaziz University, Jeddah, Saudi Arabia. alalmalki@kau.edu.sa.
Mamdooh A GariCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. mgari@kau.edu.sa.
Adel M AbuzenadahCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. aabuzenadah@kau.edu.sa.
Adeel G ChaudharyCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. chaudhary@kau.edu.sa.
Mohammed H AlqahtaniCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. mhalqahtani@kau.edu.sa.
Sahira LaryBiochemistry Department, King Abdulaziz University, Jeddah, Saudi Arabia. slary@kau.edu.sa.
Farid AhmedCenter of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. fahmed1@kau.edu.sa.
Jolanta U WeaverInstitute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. Jolanta.Weaver@newcastle.ac.uk.
King Abdulaziz University · SANewcastle University · GBQueen Elizabeth Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM). To identify the most effective treatment for CVD, it is paramount to understand the mechanism behind cardioprotective therapies. Although metformin has been shown to reduce CVD in Type-2 DM clinical trials, the underlying mechanism remains unexplored. CD34(+) cell-based therapies offer a new treatment approach to CVD. The aim of this study was to investigate the effect of metformin on the angiogenic properties of CD34(+) cells under conditions mimicking acute myocardial infarction in diabetes.

methodsCD34(+) cells were cultured in 5.5 or 16.5 mmol/L glucose ± 0.01 mmol/L metformin and then additionally ± 4 % hypoxia. The paracrine function of CD34(+) cell-derived conditioned medium was assessed by measuring pro-inflammatory cytokines, vascular endothelial growth factor A (VEGFA), and using an in vitro tube formation assay for angiogenesis. Also, mRNA of CD34(+) cells was assayed by microarray and genes of interest were validated by qRT-PCR.

resultsMetformin increased in vitro angiogenesis under hyperglycemia-hypoxia and augmented the expression of VEGFA. It also reduced the angiogenic-inhibitors, chemokine (C-X-C motif) ligand 10 (CXCL10) and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNAs, which were upregulated under hyperglycemia-hypoxia. In addition metformin, increased expression of STEAP family member 4 (STEAP4) under euglycemia, indicating an anti-inflammatory effect.

conclusionsMetformin has a dual effect by simultaneously increasing VEGFA and reducing CXCL10 and TIMP1 in CD34(+) cells in a model of the diabetic state combined with hypoxia. Therefore, these angiogenic inhibitors are promising therapeutic targets for CVD in diabetic patients. Moreover, our data are commensurate with a vascular protective effect of metformin and add to the understanding of underlying mechanisms.

Indexed as

Angiogenesis Inducing AgentsAntigens, CD34BiomarkersCell HypoxiaCells, CulturedChemokine CXCL10Dose-Response Relationship, DrugDown-RegulationGene Expression ProfilingHumansHuman Umbilical Vein Endothelial CellsHyperglycemiaHypoglycemic AgentsMembrane ProteinsMetforminMyocardial InfarctionAngiogenesis Inducing AgentsAntigens, CD34BiomarkersChemokine CXCL10CXCL10 protein, humanHypoglycemic AgentsMembrane ProteinsMetforminOxidoreductasesSTEAP4 protein, humanTIMP1 protein, humanTissue Inhibitor of Metalloproteinase-1Vascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID26861446
PMCPMC4748498
OpenAlexW2277130803

What OpenQuestion holds

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LicenceCC BY
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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.