Evidence map›Paper›PMID 38489029›Full record

ArticleDiabetologia2024

Circulating small extracellular vesicles mediate vascular hyperpermeability in diabetes.

Dakota Gustafson, Peter V DiStefano, Xue Fan Wang, Ruilin Wu, Siavash Ghaffari, Crizza Ching, Kumaragurubaran Rathnakumar, Faisal Alibhai, Michal Syonov, Jessica Fitzpatrick and 9 more

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

Article in Diabetologia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.5field-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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Review
  3. Adipose-Derived Extracellular Vesicles and Intercellular Crosstalk With Skeletal Muscle: Implications for Sarcopenic Obesity and Metabolic Dysregulation.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Immune and Metabolic Mechanisms of Endothelial Dysfunction.International journal of molecular sciences · 2024
    Review
  8. International journal of molecular sciences · 2024
    Article
  9. 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

19 authors at 3 institutions in 1 country.

Dakota Gustafson *Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-8374-6331
Peter V DiStefano *Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Xue Fan WangDivision of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
Ruilin WuToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Siavash GhaffariKeenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-8190-5674
Crizza ChingToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Kumaragurubaran RathnakumarToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Faisal AlibhaiToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Michal SyonovKeenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, ON, Canada.
Jessica FitzpatrickDepartment of Medicine and Pediatrics, Women's College Hospital, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Emilie BoudreauToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Cori LauToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Natalie GalantToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Mansoor HusainToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-3740-6739
Ren-Ke LiToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-2584-060X
Warren L LeeDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-1788-6587
Rulan S ParekhDepartment of Medicine and Pediatrics, Women's College Hospital, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.
Philippe P MonnierDivision of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-6221-4130
Jason E FishToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada. Jason.Fish@utoronto.ca.ORCID http://orcid.org/0000-0003-0640-7277
University Health Network · CASt. Michael's Hospital · CAUniversity of Toronto · CA

Funding

CIHR PJT148487CIHR PJT173489
6 · The paper itself

Abstract

aims/hypothesisA hallmark chronic complication of type 2 diabetes mellitus is vascular hyperpermeability, which encompasses dysfunction of the cerebrovascular endothelium and the subsequent development of associated cognitive impairment. The present study tested the hypothesis that during type 2 diabetes circulating small extracellular vesicles (sEVs) exhibit phenotypic changes that facilitate pathogenic disruption of the vascular barrier.

methodssEVs isolated from the plasma of a mouse model of type 2 diabetes and from diabetic human individuals were characterised for their ability to disrupt the endothelial cell (EC) barrier. The contents of sEVs and their effect on recipient ECs were assessed by proteomics and identified pathways were functionally interrogated with small molecule inhibitors.

resultsUsing intravital imaging, we found that diabetic mice (Lepr CONCLUSIONS/

interpretationDiabetes is associated with marked increases in the concentration and size of circulating sEVs. The modulation of sEV-associated proteins under diabetic conditions can induce vascular leak through activation of the MEK/ROCK pathway. These data identify a new paradigm by which diabetes can induce hyperpermeability and dysfunction of the cerebrovasculature and may implicate sEVs in the pathogenesis of cognitive decline during type 2 diabetes.

Indexed as

Capillary PermeabilityDiabetes Mellitus, Type 2Extracellular VesiclesAnimalsDiabetes Mellitus, ExperimentalEndothelial CellsEndothelium, VascularHumansMaleMiceMice, Inbred C57BLProteomicsCerebrovasculatureCognitive impairmentDiabetesEndothelial dysfunctionExtracellular vesiclesPermeabilityType 2 DiabetesVascular biologyVascular hyperpermeabilityVasculature

Identifiers

PMID38489029
PMCPMC11058313
OpenAlexW4392864567

What OpenQuestion 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 OpenQuestion graph.