Evidence map›Paper›PMID 38517482›Full record

ArticleBasic research in cardiology2024

Identification of a mechanism promoting mitochondrial sterol accumulation during myocardial ischemia-reperfusion: role of TSPO and STAR.

Juliette Bréhat, Shirin Leick, Julien Musman, Jin Bo Su, Nicolas Eychenne, Frank Giton, Michael Rivard, Louis-Antoine Barel, Chiara Tropeano, Frederica Vitarelli and 5 more

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Article in Basic research in cardiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
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

6 citing papers in PubMed, 11 citations in OpenAlex.

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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

15 authors at 6 institutions in 2 countries.

Juliette Bréhat *INSERM U955-IMRB, Team Ghaleh, UPEC, Ecole Nationale Vétérinaire d'Alfort, Faculté de Santé, 8 rue du général Sarrail, 94000, Créteil, France.
Shirin Leick *INSERM U955-IMRB, Team Ghaleh, UPEC, Ecole Nationale Vétérinaire d'Alfort, Faculté de Santé, 8 rue du général Sarrail, 94000, Créteil, France.
Julien MusmanINSERM U955-IMRB, Team Ghaleh, UPEC, Ecole Nationale Vétérinaire d'Alfort, Faculté de Santé, 8 rue du général Sarrail, 94000, Créteil, France.
Jin Bo SuINSERM U955-IMRB, Team Ghaleh, UPEC, Ecole Nationale Vétérinaire d'Alfort, Faculté de Santé, 8 rue du général Sarrail, 94000, Créteil, France.
Nicolas EychenneCHIV, Villeneuve-Saint-Georges, France.
Frank GitonPôle Biologie-Pathologie, IMRB U955, Hôpital Henri Mondor, Créteil, France.
Michael RivardCNRS, ICMPE, UMR 7182, UPEC, Thiais, France.
Louis-Antoine BarelCNRS, ICMPE, UMR 7182, UPEC, Thiais, France.
Chiara TropeanoLaboratory of Clinical Chemistry, ASST-Brianza Department of Medicine and Surgery, Hospital Pio XI Desio, University of Milano Bicocca, Monza, Italy.
Frederica VitarelliLaboratory of Clinical Chemistry, ASST-Brianza Department of Medicine and Surgery, Hospital Pio XI Desio, University of Milano Bicocca, Monza, Italy.
Claudio CacciaUnit of Medical Genetics and Neurogenetics, Istituto Neurologico Carlo Besta, Fondazione IRCCS, Milan, Italy.
Valerio LeoniLaboratory of Clinical Chemistry, ASST-Brianza Department of Medicine and Surgery, Hospital Pio XI Desio, University of Milano Bicocca, Monza, Italy.
Bijan GhalehINSERM U955-IMRB, Team Ghaleh, UPEC, Ecole Nationale Vétérinaire d'Alfort, Faculté de Santé, 8 rue du général Sarrail, 94000, Créteil, France.
Sandrine PonsINSERM U955-IMRB, Team Ghaleh, UPEC, Ecole Nationale Vétérinaire d'Alfort, Faculté de Santé, 8 rue du général Sarrail, 94000, Créteil, France.
Didier MorinINSERM U955-IMRB, Team Ghaleh, UPEC, Ecole Nationale Vétérinaire d'Alfort, Faculté de Santé, 8 rue du général Sarrail, 94000, Créteil, France. didier.morin@inserm.fr.ORCID 0000-0002-0967-1850
Inserm · FRUniversity of Milano-Bicocca · ITCentre National de la Recherche Scientifique · FRCentre Hospitalier Intercommunal de Villeneuve-Saint-Georges · FRFondazione IRCCS Istituto Neurologico Carlo Besta · ITUniversité Paris-Est Créteil · FR

Funding

Fondation de France 2018-00086493Ministère de l'enseignement supérieur, de la recherche et de l'innovation 2013-141Ministère de l'enseignement supérieur, de la recherche et de l'innovation 2018-057
6 · The paper itself

Abstract

Hypercholesterolemia is a major risk factor for coronary artery diseases and cardiac ischemic events. Cholesterol per se could also have negative effects on the myocardium, independently from hypercholesterolemia. Previously, we reported that myocardial ischemia-reperfusion induces a deleterious build-up of mitochondrial cholesterol and oxysterols, which is potentiated by hypercholesterolemia and prevented by translocator protein (TSPO) ligands. Here, we studied the mechanism by which sterols accumulate in cardiac mitochondria and promote mitochondrial dysfunction. We performed myocardial ischemia-reperfusion in rats to evaluate mitochondrial function, TSPO, and steroidogenic acute regulatory protein (STAR) levels and the related mitochondrial concentrations of sterols. Rats were treated with the cholesterol synthesis inhibitor pravastatin or the TSPO ligand 4'-chlorodiazepam. We used Tspo deleted rats, which were phenotypically characterized. Inhibition of cholesterol synthesis reduced mitochondrial sterol accumulation and protected mitochondria during myocardial ischemia-reperfusion. We found that cardiac mitochondrial sterol accumulation is the consequence of enhanced influx of cholesterol and not of the inhibition of its mitochondrial metabolism during ischemia-reperfusion. Mitochondrial cholesterol accumulation at reperfusion was related to an increase in mitochondrial STAR but not to changes in TSPO levels. 4'-Chlorodiazepam inhibited this mechanism and prevented mitochondrial sterol accumulation and mitochondrial ischemia-reperfusion injury, underlying the close cooperation between STAR and TSPO. Conversely, Tspo deletion, which did not alter cardiac phenotype, abolished the effects of 4'-chlorodiazepam. This study reveals a novel mitochondrial interaction between TSPO and STAR to promote cholesterol and deleterious sterol mitochondrial accumulation during myocardial ischemia-reperfusion. This interaction regulates mitochondrial homeostasis and plays a key role during mitochondrial injury.

Indexed as

Mitochondria, HeartMyocardial Reperfusion InjuryPhosphoproteinsAnimalsBenzodiazepinonesCarrier ProteinsCholesterolDisease Models, AnimalRatsRats, WistarReceptors, GABAReceptors, GABA-ASteroidogenic Acute Regulatory Protein4'-chlorodiazepamBenzodiazepinonesCarrier ProteinsCholesterolPhosphoproteinsReceptors, GABAReceptors, GABA-ASteroidogenic Acute Regulatory ProteinTspo protein, ratMitochondriaMyocardial ischemia–reperfusionSteroidogenic acute regulatory proteinTranslocator protein

Identifiers

PMID38517482
OpenAlexW4393072722

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.