Evidence map›Paper›PMID 37024132›Full record

ArticleThe European respiratory journal2023

Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension.

Ananya Chakraborty, Abinaya Nathan, Mark Orcholski, Stuti Agarwal, Elya A Shamskhou, Natasha Auer, Ankita Mitra, Eleana Stephanie Guardado, Gowri Swaminathan, David F Condon and 22 more

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

Article in The European respiratory journal, 2023. 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
4.4field-weighted citation impact, top 5% 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, 17 citations in OpenAlex.

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  4. Combined impact of ROR2 and its ligands on the pathogenesis and prognosis of idiopathic pulmonary fibrosis.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors at 16 institutions in 3 countries.

Ananya ChakrabortyDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Abinaya NathanDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Mark OrcholskiDepartment of Medicine, University of Laval, Quebec City, QC, Canada.
Stuti AgarwalDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Elya A ShamskhouUniversity of Washington, Seattle, WA, USA.
Natasha AuerDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Ankita MitraDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Eleana Stephanie GuardadoDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Gowri SwaminathanDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
David F CondonDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Joyce YuDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Matthew McCarraDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Nicholas H JuulDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.
Alden MalloryUniversity of Colorado, Boulder, CO, USA.
Roberto A Guzman-HernandezUniversity of Puerto Rico Medical School, San Juan, PR, USA.ORCID 0000-0003-0825-7655
Ke YuanBoston Children's Hospital, Boston, MA, USA.
Vanesa RojasUniversity of Nevada, Las Vegas, NV, USA.
Joseph T CrossnoPulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Lai-Ming YungBrigham and Women's Hospital, Boston, MA, USA.
Paul B YuBrigham and Women's Hospital, Boston, MA, USA.
Thomas SpencerWashington State University, Pullman, WA, USA.
Robert A WinnMassey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Andrea FrumpIndiana University, Indianapolis, IN, USA.
Vijaya KaroorNational Jewish Center, Denver, CO, USA.
Tim LahmNational Jewish Center, Denver, CO, USA.
Haley HedlinDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA.ORCID 0000-0002-0757-7959
Jeffrey R FinemanDepartment of Pediatrics and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Robert LafyatisDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-9398-5034
Carsten N F KnutsenDivision of Pediatric Critical Care Medicine, Stanford University, Palo Alto, CA, USA.
Cristina M AlviraDivision of Pediatric Critical Care Medicine, Stanford University, Palo Alto, CA, USA.
David N CornfieldDivision of Pediatric Pulmonary and Critical Care Medicine, Stanford University, Palo Alto, CA, USA.
Vinicio A de Jesus PerezDivision of Pulmonary and Critical Care, Stanford University, Palo Alto, CA, USA vdejesus@stanford.edu.
Stanford University · USBrigham and Women's Hospital · USNational Jewish Health · USPalo Alto University · USBoston Children's Hospital · USIndiana University – Purdue University Indianapolis · USUniversité Laval · CAUniversity of California, San Francisco · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Colorado Boulder · USUniversity of Nevada, Las Vegas · USUniversity of Pittsburgh · USUniversity of Puerto Rico, Medical Sciences Campus · PRUniversity of Washington · USVirginia Commonwealth University · USWashington State University · US

Funding

Systems Biology CoreP50AR080612 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROBERT A. LAFYATIS · 2022 to 2026
$9.5M
The Wnt7a/ROR2 axis in the pathogenesis of pulmonary arterial hypertensionR01HL134776 · NHLBI · STANFORD UNIVERSITY · PI DE JESUS PEREZ, VINICIO A · 2017 to 2025
$5.0M
Endothelial-pericyte interactions in the pathogenesis of pulmonary arterial hypertensionR01HL139664 · NHLBI · STANFORD UNIVERSITY · PI DE JESUS PEREZ, VINICIO A · 2018 to 2025
$4.7M
Mechanisms of Right Ventricle Adaptation to Pulmonary HypertensionR01HL144727 · NHLBI · NATIONAL JEWISH HEALTH · PI Tim Lahm · 2019 to 2026
$4.7M
The emerging role of apelin, RAAS, and ACE2 crosstalk in pulmonary hypertensionR01HL164791 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI Andrea Lee Frump · 2022 to 2026
$3.8M
Case-Control Study of Methamphetamine in Pulmonary Arterial HypertensionR01HL159886 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KAWUT, STEVEN M, ZAMANIAN, ROHAM · 2021 to 2025
$3.7M
Context-specific angiogenic signaling in the pulmonary vasculatureR01HL159443 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI YU, PAUL B · 2021 to 2024
$2.4M
Pericyte contribution to capillary remodeling in pulmonary arterial hypertensionR01HL171405 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Juan M Melero-Martin, Ke Yuan · 2024 to 2026
$2.4M
Pericytes differentiate into smooth muscle cells through HIF2a/SDF1 activationR01HL150106 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI YUAN, KE · 2021 to 2025
$2.2M
American Heart Association-American Stroke Association 15SDG25710448BLRD VA I01 BX002042NHLBI NIH HHS R01 HL134776NHLBI NIH HHS R01 HL139664NHLBI NIH HHS R01 HL144727NHLBI NIH HHS R01 HL150106NHLBI NIH HHS R01 HL159443NHLBI NIH HHS R01 HL159886NHLBI NIH HHS R01 HL164791NHLBI NIH HHS R01 HL171405NIAMS NIH HHS P50 AR080612
6 · The paper itself

Abstract

introductionPulmonary arterial hypertension (PAH) is characterised by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH is incompletely understood. We hypothesised that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis, and its loss contributes to PAH.

methodsLung tissue and PMVECs from healthy and PAH patients were screened for Wnt production. Global and endothelial-specific

resultsHealthy PMVECs demonstrated >6-fold Wnt7a expression during angiogenesis that was absent in PAH PMVECs and lungs. Wnt7a expression correlated with the formation of tip cells, a migratory endothelial phenotype critical for angiogenesis. PAH PMVECs demonstrated reduced vascular endothelial growth factor (VEGF)-induced tip cell formation as evidenced by reduced filopodia formation and motility, which was partially rescued by recombinant Wnt7a. We discovered that Wnt7a promotes VEGF signalling by facilitating Y1175 tyrosine phosphorylation in vascular endothelial growth factor receptor 2 (VEGFR2) through receptor tyrosine kinase-like orphan receptor 2 (ROR2), a Wnt-specific receptor. We found that ROR2 knockdown mimics Wnt7a insufficiency and prevents recovery of tip cell formation with Wnt7a stimulation. While there was no difference between wild-type and endothelial-specific

conclusionsWnt7a promotes VEGF signalling in lung PMVECs and its loss is associated with an insufficient VEGF-A angiogenic response. We propose that Wnt7a deficiency contributes to progressive small vessel loss in PAH.

Indexed as

Pulmonary Arterial HypertensionAnimalsEndothelial CellsFamilial Primary Pulmonary HypertensionHypoxiaMiceVascular Endothelial Growth Factor AVascular Endothelial Growth Factor A

Identifiers

PMID37024132
PMCPMC10259331
OpenAlexW4362665150

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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.