Evidence map›Paper›PMID 31921855›Full record

ArticleFrontiers in cell and developmental biology2019

Extracellular Vesicles From Pathological Microenvironment Induce Endothelial Cell Transformation and Abnormal Angiogenesis via Modulation of TRPV4 Channels.

Brianna D Guarino, Ravi K Adapala, Anantha K Kanugula, Nina M Lenkey, Julie A Dougherty, Sailaja Paruchuri, Mahmood Khan, Charles K Thodeti

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cell and developmental biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Biogenesis and functional implications of extracellular vesicles in cancer metastasis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review
  3. Review
  4. Review
  5. Review
  6. Studying Angiogenesis Using Matrigel In Vitro and In Vivo.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Tumor-Derived Extracellular Vesicles Induce Abnormal AngiogenesisFrontiers in bioengineering and biotechnology · 2021
    Article
  13. Review
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

8 authors at 4 institutions in 1 country.

Brianna D GuarinoDepartment of Integrative Medical Sciences, College of Medicine, Northeast Ohio Medical University, Rootstown, OH, United States.
Ravi K AdapalaDepartment of Integrative Medical Sciences, College of Medicine, Northeast Ohio Medical University, Rootstown, OH, United States.
Anantha K KanugulaDepartment of Integrative Medical Sciences, College of Medicine, Northeast Ohio Medical University, Rootstown, OH, United States.
Nina M LenkeyDepartment of Integrative Medical Sciences, College of Medicine, Northeast Ohio Medical University, Rootstown, OH, United States.
Julie A DoughertyDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Sailaja ParuchuriDepartment of Chemistry, The University of Akron, Akron, OH, United States.
Mahmood KhanDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Charles K ThodetiDepartment of Integrative Medical Sciences, College of Medicine, Northeast Ohio Medical University, Rootstown, OH, United States.
Northeast Ohio Medical University · USKent State University · USThe Ohio State University Wexner Medical Center · USUniversity of Akron · US

Funding

Biomimetic cardiac patch capable of rapid angiogenesisR01HL136232 · NHLBI · OHIO STATE UNIVERSITY · PI KHAN, MAHMOOD · 2017 to 2021
$2.8M
Mechanical Control of Coronary Angiogenesis in Myocardial Adaptation to IschemiaR01HL148585 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI THODETI, CHARLES K · 2019 to 2022
$1.8M
Mechanotransduction in myocardial adaptation to ischemiaR01HL119705 · NHLBI · NORTHEAST OHIO MEDICAL UNIVERSITY · PI THODETI, CHARLES K · 2015 to 2018
$1.5M
Integration of Mechanical and Soluble Signaling in Tumor AngiogenesisR15CA202847 · NCI · NORTHEAST OHIO MEDICAL UNIVERSITY · PI THODETI, CHARLES K · 2016 to 2016
$453k
Post-Infarction Remodeling in the Diabetic MyocardiumR15HL106442 · NHLBI · NORTHEAST OHIO MEDICAL UNIVERSITY · PI MESZAROS, J GARY, THODETI, CHARLES K · 2012 to 2012
$444k
NCI NIH HHS R15 CA202847NHLBI NIH HHS R01 HL119705NHLBI NIH HHS R01 HL136232NHLBI NIH HHS R01 HL148585NHLBI NIH HHS R15 HL106442
6 · The paper itself

Abstract

The soluble and mechanical microenvironment surrounding endothelial cells influences and instructs them to form new blood vessels. The cells in the pathological tumor microenvironment release extracellular vesicles (EVs) for paracrine signaling. EVs have been shown to induce angiogenesis by communicating with endothelial cells, but the underlying molecular mechanisms are not well known. We have recently shown that the mechanosensitive ion channel transient receptor vanilloid 4 (TRPV4) expression and activity is significantly reduced in tumor endothelial cells (TEC), and that activation of TRPV4 normalized the tumor vasculature and improved cancer therapy. However, whether and how the tumor microenvironment downregulates TRPV4 and transforms the normal endothelial cell phenotype remains unknown. To explore this, we exposed normal human endothelial cells (hNEC) to human lung tumor cell conditioned media (TCM) and measured phenotypic changes and angiogenesis. We found that treatment with TCM transformed hNEC to a TEC-like phenotype (hTEC) as evidenced by increased expression of tumor endothelial cell marker 8 (TEM8) and exhibition of abnormal angiogenesis on 2D-Matrigels compared to normal hNEC. Mechanistically, expression and activity of TRPV4 was decreased in hTEC. Further, when pre-treated with exosome inhibitor GW4869, TCM failed to induce hNEC transformation to hTEC. Finally, addition of purified EVs from TCM induced transformation of hNEC to hTEC as evidenced by abnormal angiogenesis

Indexed as

angiogenesisendothelial cellsextracellular vesiclesTRPV4tumor

Identifiers

PMID31921855
PMCPMC6928002
OpenAlexW2996377533

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.