Evidence map›Paper›PMID 39001626›Full record

ArticleAdvanced healthcare materials2024

Hypoxic-Normoxic Crosstalk Activates Pro-Inflammatory Signaling in Human Cardiac Fibroblasts and Myocytes in a Post-Infarct Myocardium on a Chip.

Natalie N Khalil, Megan L Rexius-Hall, Divya Gupta, Liam McCarthy, Riya Verma, Austin C Kellogg, Kaelyn Takamoto, Maryann Xu, Tiana Nejatpoor, Sarah J Parker and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced healthcare materials, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
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

11 authors.

Natalie N KhalilAlfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
Megan L Rexius-HallAlfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA.ORCID 0000-0003-1908-6783
Divya GuptaDepartment of Biomedical Sciences and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Liam McCarthyDepartment of Biomedical Sciences and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Riya VermaDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90033, USA.
Austin C KelloggAlfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
Kaelyn TakamotoAlfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
Maryann XuAlfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
Tiana NejatpoorAlfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
Sarah J ParkerDepartment of Biomedical Sciences and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Megan L McCainAlfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA.

Funding

Engineering a Microphysiological System to Model the Infarct Border Zone and Interrogate Oxygen-Dependent Cell-Cell Communication in the MyocardiumR01HL153286 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Megan Laura McCain · 2020 to 2026
$3.4M
Microphysiological Systems to Study Hypoxic Cardiac InjuryR00HL157722 · NHLBI · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · PI Megan L. Rexius · 2025 to 2026
$498k
Microphysiological Systems to Study Hypoxic Cardiac InjuryK99HL157722 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI REXIUS, MEGAN L. · 2023 to 2024
$238k
Additional Ventures 1159088National Science Foundation Graduate Research Fellowship Program DGE-1842487NHLBI NIH HHS K99 HL157722NHLBI NIH HHS R00 HL157722NHLBI NIH HHS R01 HL153286NHLBI NIH HHS R01HL153286
6 · The paper itself

Abstract

Myocardial infarctions locally deprive myocardium of oxygenated blood and cause immediate cardiac myocyte necrosis. Irreparable myocardium is then replaced with a scar through a dynamic repair process that is an interplay between hypoxic cells of the infarct zone and normoxic cells of adjacent healthy myocardium. In many cases, unresolved inflammation or fibrosis occurs for reasons that are incompletely understood, increasing the risk of heart failure. Crosstalk between hypoxic and normoxic cardiac cells is hypothesized to regulate mechanisms of repair after a myocardial infarction. To test this hypothesis, microfluidic devices are fabricated on 3D printed templates for co-culturing hypoxic and normoxic cardiac cells. This system demonstrates that hypoxia drives human cardiac fibroblasts toward glycolysis and a pro-fibrotic phenotype, similar to the anti-inflammatory phase of wound healing. Co-culture with normoxic fibroblasts uniquely upregulates pro-inflammatory signaling in hypoxic fibroblasts, including increased secretion of tumor necrosis factor alpha (TNF-α). In co-culture with hypoxic fibroblasts, normoxic human induced pluripotent stem cell (hiPSC)-derived cardiac myocytes also increase pro-inflammatory signaling, including upregulation of interleukin 6 (IL-6) family signaling pathway and increased expression of IL-6 receptor. Together, these data suggest that crosstalk between hypoxic fibroblasts and normoxic cardiac cells uniquely activates phenotypes that resemble the initial pro-inflammatory phase of post-infarct wound healing.

Indexed as

Coculture TechniquesFibroblastsLab-On-A-Chip DevicesMyocardial InfarctionMyocytes, CardiacSignal TransductionCell HypoxiaHumansInduced Pluripotent Stem CellsInflammationInterleukin-6MyocardiumTumor Necrosis Factor-alphaInterleukin-6Tumor Necrosis Factor-alphacardiac fibrosiscrosstalkhypoxiamyocardial infarctionorgan‐on‐a‐chip

Identifiers

PMID39001626
PMCPMC11560646

What OpenQuestion holds

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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.