ArticleCell communication and signaling : CCS2026
Neddylation blockade protects endothelial cells against inflammation and ischemia-reperfusion injuries.
Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
backgroundLong-term allograft survival is limited by the occurrence of chronic allograft dysfunction, mainly due to antibody mediated rejection and aspecific fibrosis. The latter is favored by ischemia-reperfusion injury (IRI), particularly in organs from extended criteria donors and from donors after cardiocirculatory arrest. The graft endothelium is highly sensitive to IRI that causes chronic damages and increases its immunogenicity. Thus, improvement of preservation methods and the treatment of organs prior to implantation (so called "graft preconditioning") constitute a major clinical challenge to improve graft survival. Among the mechanisms implicated in the reactivity of endothelial cells, neddylation has emerged as a potential candidate of interest.
methodsTo study the potential of neddylation blockade as a preconditioning strategy, we used an in vitro model of microvascular endothelial cells (ECs) treated in conditions close to those of organ transplant preservation. ECs were subjected to hypothermic preservation (4 °C) in the presence of the neddylation inhibitor MLN4924, and following rewarming (37 °C), stimulated with TNAα and IFNγ to mimic sterile inflammation at reperfusion.
resultsWe found that preconditioning of ECs with MLN4924 had potent anti-inflammatory effects by blocking the induction of adhesion molecules (ICAM1, VCAM1, E-Selectin), of HLA class I and II, and of the pro-inflammatory cytokines and chemokines IL6, RANTES and Fractalkine. Functionally, this translated into inhibition of EC-mediated T lymphocyte activation and of T cell adhesion to ECs. MLN4924 preconditioning also blocked the induction of prothrombotic molecules (Tissue Factor and PAI-1), and platelet adhesion to ECs. Finally, MLN4924 enhanced the expression of the complement inhibitor CD55 and of the antioxidant molecule HO-1, and protected ECs from hypothermia and hypoxia induced cell death.
conclusionsOur results identify the neddylation inhibitor MLN4924 as a powerful protective molecule for endothelial cells and a promising candidate for graft preconditioning and protection of organs against IRI.
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.