Evidence map›Paper›PMID 40203840›Full record

ArticleFundamental & clinical pharmacology2025

Dual ET

Francesca Lockwood, Marianne Lachaux, Najah Harouki, Matthieu Soulié, Lionel Nicol, Sylvanie Renet, Anaïs Dumesnil, Magali Vercauteren, Jeremy Bellien, Marc Iglarz and 2 more

Abstract read
In one paragraph

Article in Fundamental & clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Dual ETFundamental & clinical pharmacology · 2025
    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

12 authors.

Francesca LockwoodUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.ORCID https://orcid.org/0000-0002-8426-9589
Marianne LachauxUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.
Najah HaroukiUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.
Matthieu SouliéUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.
Lionel NicolUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.
Sylvanie RenetUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.
Anaïs DumesnilUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.
Magali VercauterenIdorsia Pharmaceuticals Ltd., Allschwil, Switzerland.
Jeremy BellienUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.
Marc IglarzIdorsia Pharmaceuticals Ltd., Allschwil, Switzerland.
Vincent RichardUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.
Paul MulderUniv Rouen Normandie, INSERM U1096, EnVI, Rouen, France.

Funding

Actelion PharmaceuticalsActelion Pharmaceuticals Ltd.Erasmus student fundingEuropean Fibro-Targets Project FP7#602904European UnionEuropean Union and the Région NormandieFédération Française de CardiologieFP7-funded COST ADMIRE network BM1301Région NormandieWinningNormandy Marie Skłodowska-Curie postdoc fellowship 101034329WinningNormandy Marie Skłodowska-Curie post-doc fellowship H2020-MSCA-COFUND-2020, Marie Skłodowska-Curie grant agreement N°101034329
6 · The paper itself

Abstract

backgroundMetabolic syndrome (MetS) is a multifaceted disease associated with heart failure (HF), which affects the vascular system. The endothelin (ET) system is a key player in MetS and HF; therefore, targets for ET receptors are of therapeutic interest.

objectivesThis study sought to evaluate the effects of macitentan, a dual endothelin receptor antagonist (ERA), in a rat model of MetS-induced heart failure with preserved ejection fraction (HFpEF).

methodsWe assessed in 12-week-old Zucker fa/fa rats the effects of macitentan (10 mg/kg/day as a food additive for short-term/7- or long-term/90-day treatment) on right ventricular (RV) and left ventricular (LV) function/remodelling (MRI), RV and LV haemodynamics (catheterization) and RV and LV coronary function (myograph).

resultsAfter 7- and 90-days, untreated Zucker fa/fa rats presented isolated LV diastolic dysfunction (illustrated by elevated LV end-diastolic pressure [EDP] and LV end-diastolic pressure-volume relationship [EDPVR] without changes in LV EDPVR). This was associated with increased collagen deposition and impaired endothelium-dependent coronary artery relaxation. Macitentan 7- and 90-day treatment significantly decreased blood pressure and prevented LV, RV and coronary dysfunctions and long-term treatment reduced LV collagen density. Moreover, 7- and 90-day macitentan treatment significantly reduced cardiac inflammation and reactive oxygen species (ROS) production.

conclusionsDual ERA macitentan improved both LV and RV diastolic dysfunction. This was associated with improved coronary vasodilation, diminished cardiac oxidative stress and improved blood composition. These results suggest that antagonizing the ET system with macitentan is a promising approach to treat HFpEF and its complications.

Indexed as

Endothelin A Receptor AntagonistsEndothelin B Receptor AntagonistsHeart FailureMetabolic SyndromePyrimidinesStroke VolumeSulfonamidesAnimalsDisease Models, AnimalMaleRatsRats, ZuckerVentricular Dysfunction, LeftVentricular Function, LeftVentricular RemodelingEndothelin A Receptor AntagonistsEndothelin B Receptor AntagonistsmacitentanPyrimidinesSulfonamidescardiac remodellingendothelinheart failuremetabolic syndrome

Identifiers

PMID40203840
PMCPMC11981691

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.