Evidence map›Paper›PMID 40643537›Full record

ArticleCells2025

The Phosphodiesterase 4 Inhibitor Roflumilast Protects Microvascular Endothelial Cells from Irradiation-Induced Dysfunctions.

Nathalie Guitard, Florent Raffin, François-Xavier Boittin

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

3 authors.

Nathalie GuitardUnité de Radiobiologie, Département Effets Biologiques des Rayonnements, IRBA (Institut de Recherche Biomédicale des Armées), 91223 Brétigny-sur-Orge, France.
Florent RaffinUnité Analyses Biologiques, Département des Plateformes, IRBA (Institut de Recherche Biomédicale des Armées), 91223 Brétigny-sur-Orge, France.
François-Xavier BoittinUnité de Radiobiologie, Département Effets Biologiques des Rayonnements, IRBA (Institut de Recherche Biomédicale des Armées), 91223 Brétigny-sur-Orge, France.

Funding

DGA (Direction Générale de l'Armement) NBC-5-NR-2322
6 · The paper itself

Abstract

In endothelial cells, high-dose irradiation induces numerous dysfunctions including alteration in junctional proteins such as VE-Cadherin, apoptosis and enhanced adhesiveness linked to overexpression of adhesion molecules like Intercellular Adhesion Molecule 1 (ICAM-1). Such endothelial dysfunctions can lead to altered tissue perfusion, development of tissue inflammation through increased endothelial permeability, and ultimately organ damage. As intracellular cyclic AMP (cAMP) levels are known to control intercellular junctions or apoptosis in the endothelium, we investigated here the effect of the Phosphodiesterase 4 inhibitor Roflumilast, a drug increasing cAMP levels, on irradiation-induced endothelial dysfunctions in human pulmonary microvascular endothelial cells (HPMECs). Using continuous impedance measurements in confluent endothelial cell monolayers, Roflumilast was found to rapidly reinforce the endothelial barrier and to prevent irradiation-induced barrier disruption. In accordance, irradiation-induced alteration in membrane VE-Cadherin-composed adherens junctions was prevented by Roflumilast treatment after irradiation, which was correlated with its protective effect of the actin cytoskeleton. Post-irradiation treatment with Roflumilast also protected HPMECs from irradiation-induced late apoptosis, but was without effect on irradiation-induced ICAM-1 overexpression. Overall, our results indicate that the beneficial effects of Roflumilast after irradiation are linked to the strengthening/protection of the endothelial barrier and reduced apoptosis, suggesting that this medicine may be useful for the treatment of endothelial damages after exposure to a high dose of radiation.

Indexed as

AminopyridinesBenzamidesEndothelial CellsMicrovesselsPhosphodiesterase 4 InhibitorsAdherens JunctionsAntigens, CDApoptosisCadherin 5CadherinsCyclic AMPCyclopropanesHumansIntercellular Adhesion Molecule-1AminopyridinesAntigens, CDBenzamidesCadherin 5CadherinsCyclic AMPCyclopropanesIntercellular Adhesion Molecule-1Phosphodiesterase 4 InhibitorsRoflumilastactin cytoskeletonapoptosisendothelial cellsICAM-1irradiationVE-Cadherin

Identifiers

PMID40643537
PMCPMC12248552

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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.