Evidence map›Paper›PMID 33086871›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2020

Defining an Upstream VEGF (Vascular Endothelial Growth Factor) Priming Signature for Downstream Factor-Induced Endothelial Cell-Pericyte Tube Network Coassembly.

Stephanie L K Bowers, Scott S Kemp, Kalia N Aguera, Gretchen M Koller, Joshua C Forgy, George E Davis

Open access · bronzeAbstract readVideo-Audio Media
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

31 citing papers in PubMed, 44 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Stephanie L K BowersFrom the Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa.
Scott S KempFrom the Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa.
Kalia N AgueraFrom the Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa.
Gretchen M KollerFrom the Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa.
Joshua C ForgyFrom the Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa.
George E DavisFrom the Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa.
University of South Florida · US

Funding

Molecular regulation of Rho and Ras family GTPase activity controls vascular lumen formation.R01HL126518 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI CLEAVER, ONDINE B, DAVIS, GEORGE E · 2015 to 2023
$3.1M
Priming of vascular tube morphogenesis: Novel role for VEGF and downstreamRhoA activationR01HL136139 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI CLEAVER, ONDINE B, DAVIS, GEORGE E · 2017 to 2020
$1.6M
Molecular basis for defective pericyte-endothelial cell interactions regulating vascular malformationsR01HL149748 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI DAVIS, GEORGE E · 2020 to 2023
$1.5M
Renal vascular remodeling and arteriogenesis: cues from smooth muscle progenitor cellsR01DK124393 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI CLEAVER, ONDINE B · 2020 to 2023
$1.4M
NHLBI NIH HHS R01 HL126518NHLBI NIH HHS R01 HL136139NHLBI NIH HHS R01 HL149748NIDDK NIH HHS R01 DK124393
6 · The paper itself

Abstract

objectiveIn this work, we have sought to define growth factor requirements and the signaling basis for different stages of human vascular morphogenesis and maturation. Approach and Results: Using a serum-free model of endothelial cell (EC) tube morphogenesis in 3-dimensional collagen matrices that depends on a 5 growth factor combination, SCF (stem cell factor), IL (interleukin)-3, SDF (stromal-derived factor)-1α, FGF (fibroblast growth factor)-2, and insulin (factors), we demonstrate that VEGF (vascular endothelial growth factor) pretreatment of ECs for 8 hours (ie, VEGF priming) leads to marked increases in the EC response to the factors which includes; EC tip cells, EC tubulogenesis, pericyte recruitment and proliferation, and basement membrane deposition. VEGF priming requires VEGFR2, and the effect of VEGFR2 is selective to the priming response and does not affect factor-dependent tubulogenesis in the absence of priming. Key molecule and signaling requirements for VEGF priming include RhoA, Rock1 (Rho-kinase), PKCα (protein kinase C α), and PKD2 (protein kinase D2). siRNA suppression or pharmacological blockade of these molecules and signaling pathways interfere with the ability of VEGF to act as an upstream primer of downstream factor-dependent EC tube formation as well as pericyte recruitment. VEGF priming was also associated with the formation of actin stress fibers, activation of focal adhesion components, upregulation of the EC factor receptors, c-Kit, IL-3Rα, and CXCR4 (C-X-C chemokine receptor type 4), and upregulation of EC-derived PDGF (platelet-derived growth factor)-BB, PDGF-DD, and HB-EGF (heparin-binding epidermal growth factor) which collectively affect pericyte recruitment and proliferation.

conclusionsOverall, this study defines a signaling signature for a separable upstream VEGF priming step, which can activate ECs to respond to downstream factors that are necessary to form branching tube networks with associated mural cells.

Indexed as

Angiogenesis Inducing AgentsCell CommunicationCells, CulturedCoculture TechniquesGene Expression RegulationHumansHuman Umbilical Vein Endothelial CellsNeovascularization, PhysiologicPericytesPhosphorylationSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Angiogenesis Inducing AgentsKDR protein, humanVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2endothelial cellsfibroblast growth factorinsulininterleukin-3stem cell factor

Identifiers

PMID33086871
PMCPMC7939123
OpenAlexW3093601476

What OpenQuestion holds

Textmetadata
LicenceTDM
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.