Evidence map›Paper›PMID 42722664›Full record

ArticleNature communications2026

A microphysiological system HHT-on-a-chip platform recapitulates patient vascular lesions.

Jennifer S Fang, Christopher J Hatch, Jillian Andrejecsk, William Van Trigt, Joshua R Gonzales, Damie J Juat, Edward K Looker, Sophia R Harris, Yu-Hsi Chen, Satomi Matsumoto and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Jennifer S FangDepartment of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California-Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0001-5703-2239
Christopher J HatchDepartment of Biomedical Engineering, Henry Samueli School of Engineering, University of California-Irvine, Irvine, CA, USA.
Jillian AndrejecskDepartment of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California-Irvine, Irvine, CA, USA.
William Van TrigtDepartment of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California-Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0003-3439-7352
Joshua R GonzalesDepartment of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California-Irvine, Irvine, CA, USA.
Damie J JuatDepartment of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California-Irvine, Irvine, CA, USA.
Edward K LookerDepartment of Cell and Molecular Biology, School of Science & Engineering, Tulane University, New Orleans, LA, USA.
Sophia R HarrisDepartment of Cell and Molecular Biology, School of Science & Engineering, Tulane University, New Orleans, LA, USA.ORCID http://orcid.org/0009-0003-6971-2655
Yu-Hsi ChenDepartment of Biomedical Engineering, Henry Samueli School of Engineering, University of California-Irvine, Irvine, CA, USA.
Satomi MatsumotoDepartment of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California-Irvine, Irvine, CA, USA.
Abraham P LeeDepartment of Biomedical Engineering, Henry Samueli School of Engineering, University of California-Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0001-8378-6616
Christopher C W HughesDepartment of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences, University of California-Irvine, Irvine, CA, USA. cchughes@uci.edu.ORCID http://orcid.org/0000-0002-3223-830X

Funding

Pilot Projects ProgramP30GM145498 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI S MICHAL JAZWINSKI · 2022 to 2026
$8.6M
Training Program in Cardiovascular Applied Research and EntrepreneurshipT32HL116270 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUGHES, CHRISTOPHER C. W. · 2013 to 2022
$1.6M
Louisiana Board of Regents (Board of Regents) 091A-24National Science Foundation (NSF) 2543698NHLBI NIH HHS T32 HL116270NIGMS NIH HHS P30 GM145498U.S. Department of Defense (United States Department of Defense) W81XWH2110108U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30GM145498U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32HL116270
6 · The paper itself

Abstract

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations (VM) focally develop in multiple organs. There are few treatment options and no cure. HHT patients inherit loss-of-function mutations affecting Alk1-Eng signaling; however, why this manifests as VMs remains poorly understood. Here we have developed a fully human cell-based microphysiological system of perfused vasculature in which inducible shRNA controls endogenous Alk1 in primary endothelial cells (EC). Resulting VMs develop over several days, recapitulate patient VM appearance, and require only a subpopulation of Alk1-deficient EC to trigger lesions. Single-cell transcriptomics suggests microvessel pruning and regression contribute to VM, while loss of PDGFB implicates mural cell recruitment. Finally, pharmacological VEGF/VEGFR inhibition blocks lesion formation. In summary, we have developed an HHT-on-a-chip model that faithfully reproduces HHT patient lesions and that can be used to better understand HHT disease biology and identify potential new HHT drugs.

Indexed as

Lab-On-A-Chip DevicesTelangiectasia, Hereditary HemorrhagicVascular MalformationsActivin Receptors, Type IActivin Receptors, Type IIEndoglinEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsMicrophysiological SystemsRNA, Small InterferingSignal TransductionVascular Endothelial Growth Factor AActivin Receptors, Type IActivin Receptors, Type IIACVRL1 protein, humanEndoglinENG protein, humanRNA, Small InterferingVascular Endothelial Growth Factor A

Identifiers

PMID42722664
PMCPMC13562586

What OpenQuestion holds

Textmetadata
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.