Evidence map›Paper›PMID 41468742›Full record

ArticleJournal of biomechanics2026

Aberrant tissue mechanics and mechanotransduction during heart development in down syndrome.

Rachel S Reeser, Mitchell C VeDepo, Rukshika S Hewawasam, Katherine A Waugh, Kyndal A Schade, Mostafa Abdel-Hafiz, Brisa Peña, Luisa Mestroni, Orfeo Sbaizero, Joaquin M Espinosa and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of biomechanics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

12 authors.

Rachel S ReeserDepartment of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Linda Crnic Institute for Down Syndrome, Colorado, Aurora, CO 80045, USA.
Mitchell C VeDepoDepartment of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Rukshika S HewawasamDepartment of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Katherine A WaughLinda Crnic Institute for Down Syndrome, Colorado, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Kyndal A SchadeLinda Crnic Institute for Down Syndrome, Colorado, Aurora, CO 80045, USA.
Mostafa Abdel-HafizDepartment of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Brisa PeñaDepartment of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Cardiovascular Institute, School of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Luisa MestroniCardiovascular Institute, School of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Orfeo SbaizeroDepartment of Engineering and Architecture, University of Trieste, Trieste, Italy.
Joaquin M EspinosaLinda Crnic Institute for Down Syndrome, Colorado, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Chelsea M MaginDepartment of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, CO 80045, USA; Department of Pediatrics, Children's Hospital Colorado, Aurora, CO 80045, USA.
Jeffrey G JacotDepartment of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Linda Crnic Institute for Down Syndrome, Colorado, Aurora, CO 80045, USA; Department of Pediatrics, Children's Hospital Colorado, Aurora, CO 80045, USA. Electronic address: jeffrey.jacot@cuanschutz.edu.

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
PRE-VASCULARIZED AND DEGRADABLE PATCHES FOR CORRECTION OF CONGENITAL HEART DEFECTSR01HL130436 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI JACOT, JEFFREY G · 2016 to 2020
$2.0M
Injectable Carbon Nanotube-Functionalized Hydrogel for miRNA DeliveryK25HL148386 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI PENA CASTELLANOS, BRISA MARISOL · 2020 to 2024
$891k
NCI NIH HHS P30 CA046934NHLBI NIH HHS K25 HL148386NHLBI NIH HHS R01 HL130436
6 · The paper itself

Abstract

Individuals with Down syndrome (DS) account for 70% of all cases of patients diagnosed with a septal heart defect. To investigate the mechanisms underlying aberrant septation in Down syndrome, we examined how altered extracellular-matrix composition and tissue stiffness in the Dp16 mouse model influence cardiomyocyte mechanotransduction using trisomy 21 iPSC-derived cardiomyocytes, revealing a potential biomechanical pathway contributing to congenital heart defects in the Down syndrome population. We hypothesized that in DS, upregulation of type VI collagen and hyaluronic acid in the endocardial cushion increases cushion stiffness, altering cellular mechanotransduction and ultimately leading to differences in cell proliferation and gene expression that perturb heart development. Results found that endocardial cushions of the Dp16 mouse model of DS showed a non-significant trend toward increased stiffness compared to WT. Furthermore, iPSC-CM with trisomy 21 exhibited decreased proliferation following culture on substrates of increasing stiffness, and following cyclic mechanical stretch, DS iPSC-CM developed stress fibers, disorganized sarcomeres and a decreased expression of mature cardiac markers. Yet cyclic mechanical stretch of control iPSC-CM induced sarcomere alignment and increased mature cardiac gene expression compared to static conditions. These data argue that tissue mechanics, driven by upregulation of ECM proteins, lead to increased endocardial cushion stiffness in the Dp16 mouse, and that iPSC-CM with trisomy 21 aberrantly respond to changes to stiffness and stretch, ultimately proposing a novel avenue to investigate congenital heart defects in the DS population.

Indexed as

Down SyndromeHeartMechanotransduction, CellularAnimalsCell ProliferationDisease Models, AnimalEndocardial CushionsExtracellular MatrixHumansInduced Pluripotent Stem CellsMiceMyocytes, CardiacCongenital heart defectsEndocardial cushionsExtracellular matrixTrisomy 21

Identifiers

PMID41468742
PMCPMC13456586

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Registered trials

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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.