Evidence map›Paper›PMID 41083055›Full record

ArticleTransplant immunology2025

Linking autophagy to endothelial cell immunogenicity in transplant-associated ischemia-reperfusion injury.

Meredith E Taylor, Dinesh Jaishankar, Krishnaraju Madavaraju, Simseok A Yuk, Kaijie Zhang, Hongzhang Mei, Connor W Lantz, Luisa H Andrade da Silva, Yu Min Lee, Jacqueline A Burke and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Transplant immunology, 2025. 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. 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

14 authors.

Meredith E TaylorComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Dinesh JaishankarComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: dinesh.jaishankar@northwestern.edu.
Krishnaraju MadavarajuComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Simseok A YukComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Kaijie ZhangDepartment of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Hongzhang MeiDepartment of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Connor W LantzComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Luisa H Andrade da SilvaComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Yu Min LeeComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Jacqueline A BurkeDeparment of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA; Querrey Simpson Institute for Regenerative Engineering, Northwestern University, Chicago, IL, USA.
Carl AtkinsonComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Bowen WangDepartment of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Evan A ScottDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
Satish N NadigComprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Querrey Simpson Institute for Regenerative Engineering, Northwestern University, Chicago, IL, USA; Departments of Microbiology-Immunology and Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: satish.nadig@nm.org.

Funding

Northwestern University Clinical and Translational Science Institute (NUCATS)TL1TR001423 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MCCOLLEY, SUSANNA A · 2015 to 2023
$5.0M
Modulating endothelial cell immunometabolism and mitochondrial morphologyimplications for organ transplantationR01AI142079 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI NADIG, SATISH N · 2019 to 2023
$1.9M
Ex vivo maintenance of endothelial cell barrier integrity via gap junction modification to prevent early ischemic injury in solid organ transplantationR21AI173763 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI NADIG, SATISH N · 2023 to 2024
$448k
NCATS NIH HHS TL1 TR001423NIAID NIH HHS R01 AI142079NIAID NIH HHS R21 AI173763
6 · The paper itself

Abstract

backgroundCold storage (CS) and ischemia-reperfusion injury (IRI) are inevitable consequences of heart transplantation (HTx), primarily affecting the microvascular endothelial cells (ECs) of donor hearts. The nutrient deprivation and oxidative stresses sustained by ECs during CS and IRI activate and trigger alloimmune recognition. ECs adapt to these conditions by utilizing autophagy to maintain cellular homeostasis. Whether autophagy plays a role in EC activation and immunogenicity during CS and IRI in HTx remains unknown.

methodsAutophagy in murine microvascular cardiac endothelial cells (MCEC) was modulated by genetic (knockout of the autophagy-related gene 5 (Atg5) by CRISPR/Cas9 technology) or pharmacological (rapamycin to induce autophagy and chloroquine to inhibit autophagy) approaches or by nanocarriers encapsulating rapamycin. MCECs were subjected to a previously established cold storage-warm reperfusion (CS-WR) model to mimic CS and IRI. We evaluated a) changes in autophagy by immunoblotting and confocal imaging, b) MCEC activation via pro-inflammatory cytokine and chemokine secretion by ELISA, and c) MCEC immunogenicity by determining T-cell activation in EC-T-cell co-cultures with MCEC-sensitized CD8

resultsAutophagy was reduced in MCECs when subjected to CS alone in organ preservation solution and increased early on during WR. The absence of the autophagic machinery in Atg5

conclusionsA novel role of autophagy in MCEC immunogenicity during CS and IRI is implicated. A viable preconditioning approach has also been demonstrated to bolster MCEC autophagy with nanocarriers during CS and mitigate its immunogenicity.

Indexed as

AutophagyCD8-Positive T-LymphocytesEndothelial CellsHeart TransplantationReperfusion InjuryAnimalsAutophagy-Related Protein 5Cells, CulturedHumansLymphocyte ActivationMaleMiceMice, Inbred C57BLMice, KnockoutOrgan PreservationSirolimusAtg5 protein, mouseAutophagy-Related Protein 5SirolimusAntigen presentationAutophagyEndothelial cellsHeart transplantationIschemia-reperfusion injury

Identifiers

PMID41083055
PMCPMC12576910

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.