Evidence map›Paper›PMID 38416823›Full record

ArticleScience advances2024

Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays.

Cassandra L Clift, Mark C Blaser, Willem Gerrits, Mandy E Turner, Abhijeet Sonawane, Tan Pham, Jason L Andresen, Owen S Fenton, Joshua M Grolman, Alesandra Campedelli and 9 more

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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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

19 authors.

Cassandra L CliftDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-2441-4251
Mark C BlaserDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-3923-9786
Willem GerritsDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Mandy E TurnerDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-6431-5077
Abhijeet SonawaneDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1166-6479
Tan PhamDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Jason L AndresenKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Owen S FentonDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-5585-9280
Joshua M GrolmanJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02134, USA.ORCID 0000-0001-5418-7235
Alesandra CampedelliDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0009-0004-2893-5892
Fabrizio BuffoloDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-9363-0199
Frederick J SchoenDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-5912-7300
Jesper HjortnaesDepartment of Cardiothoracic Surgery, Leiden University Medical Center (LUMC), Leiden, Netherlands.ORCID 0000-0002-6722-918X
Jochen D MuehlschlegelDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-6209-7253
David J MooneyJohn A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02134, USA.ORCID 0000-0001-6299-1194
Masanori AikawaDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Sasha A SinghDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-0929-3164
Robert LangerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0003-4255-0492
Elena AikawaDivision of Cardiovascular Medicine, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-7835-2135

Funding

Improving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6M
Cardiac Exosomes in myocardial Ischemic injuryR01HL150401 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MUEHLSCHLEGEL, JOCHEN DANIEL · 2020 to 2024
$3.3M
Macrophage-derived microcalcificaitonsR01HL136431 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2017 to 2020
$2.7M
New driver of fibrosis and calcification in CAVDR01HL147095 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2019 to 2022
$2.4M
NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917NHLBI NIH HHS R01 HL147095NHLBI NIH HHS R01 HL150401
6 · The paper itself

Abstract

In calcific aortic valve disease (CAVD), mechanosensitive valvular cells respond to fibrosis- and calcification-induced tissue stiffening, further driving pathophysiology. No pharmacotherapeutics are available to treat CAVD because of the paucity of (i) appropriate experimental models that recapitulate this complex environment and (ii) benchmarking novel engineered aortic valve (AV)-model performance. We established a biomaterial-based CAVD model mimicking the biomechanics of the human AV disease-prone fibrosa layer, three-dimensional (3D)-bioprinted into 96-well arrays. Liquid chromatography-tandem mass spectrometry analyses probed the cellular proteome and vesiculome to compare the 3D-bioprinted model versus traditional 2D monoculture, against human CAVD tissue. The 3D-bioprinted model highly recapitulated the CAVD cellular proteome (94% versus 70% of 2D proteins). Integration of cellular and vesicular datasets identified known and unknown proteins ubiquitous to AV calcification. This study explores how 2D versus 3D-bioengineered systems recapitulate unique aspects of human disease, positions multiomics as a technique for the evaluation of high throughput-based bioengineered model systems, and potentiates future drug discovery.

Indexed as

Aortic ValveAortic Valve StenosisCalcinosisCells, CulturedHumansProteomeProteomicsProteome

Identifiers

PMID38416823
PMCPMC10901368

What OpenQuestion holds

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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.