Evidence map›Paper›PMID 34895263›Full record

ArticleJournal of translational medicine2021

Sex-related differences of early cardiac functional and proteomic alterations in a rat model of myocardial ischemia.

Bálint András Barta, Mihály Ruppert, Klemens Erwin Fröhlich, Miguel Cosenza-Contreras, Attila Oláh, Alex Ali Sayour, Krisztián Kovács, Gellért Balázs Karvaly, Martin Biniossek, Béla Merkely and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2021. 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
0.4field-weighted citation impact, top 40% 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, 8 citations in OpenAlex.

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  4. Sex differences in proteomics of cardiovascular disease -International journal of cardiology. Heart & vasculature · 2025
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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

12 authors at 2 institutions in 2 countries.

Bálint András BartaExperimental Research Laboratory, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Városmajor u. 68, Budapest, 1122, Hungary. barta.balint@gmail.com.ORCID 0000-0001-5619-0438
Mihály RuppertExperimental Research Laboratory, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Városmajor u. 68, Budapest, 1122, Hungary.
Klemens Erwin FröhlichInstitute of Surgical Pathology, Faculty of Medicine, University of Freiburg Medical Center, Freiburg, Germany.
Miguel Cosenza-ContrerasInstitute of Surgical Pathology, Faculty of Medicine, University of Freiburg Medical Center, Freiburg, Germany.
Attila OláhExperimental Research Laboratory, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Városmajor u. 68, Budapest, 1122, Hungary.
Alex Ali SayourExperimental Research Laboratory, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Városmajor u. 68, Budapest, 1122, Hungary.
Krisztián KovácsDepartment of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Gellért Balázs KarvalyDepartment of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Martin BiniossekCenter for Biological Systems Analysis, University of Freiburg, Freiburg, Germany.
Béla MerkelyExperimental Research Laboratory, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Városmajor u. 68, Budapest, 1122, Hungary.
Oliver Schilling *Institute of Surgical Pathology, Faculty of Medicine, University of Freiburg Medical Center, Freiburg, Germany.
Tamás Radovits *Experimental Research Laboratory, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Városmajor u. 68, Budapest, 1122, Hungary.
Semmelweis University · HUUniversity of Freiburg · DE

Funding

Deutsche Forschungsgemeinschaft GR 4553/5-1Deutsche Forschungsgemeinschaft GRK 2606 "ProtPath"Deutsche Forschungsgemeinschaft INST 39/1244-1 (P12)Deutsche Forschungsgemeinschaft INST 39/766-3 (Z1)Deutsche Forschungsgemeinschaft PA 2807/3-1Deutsche Forschungsgemeinschaft SCHI 871/11-1Deutsche Forschungsgemeinschaft SCHI 871/15-1Deutschen Konsortium für Translationale Krebsforschung project Impro-RecERA PerMed programme 01KU1915AERA PerMed programme 01KU1916ERA PerMed programme BMBFGerman-Israeli Foundation for Scientific Research and Development grant no. 1444Nemzeti Kutatási, Fejlesztési és Innovaciós Alap 2020-4.1.1.-TKP2020Nemzeti Kutatási, Fejlesztési és Innovaciós Alap K134939Nemzeti Kutatási, Fejlesztési és Innovaciós Alap NVKP_16-1-2016-0017Nemzeti Kutatási, Fejlesztési és Innovaciós Alap ÚNKP-20-3-I-SE-1
6 · The paper itself

Abstract

backgroundReduced cardiovascular risk in premenopausal women has been the focus of research in recent decades. Previous hypothesis-driven experiments have highlighted the role of sex hormones on distinct inflammatory responses, mitochondrial proteins, extracellular remodeling and estrogen-mediated cardioprotective signaling pathways related to post-ischemic recovery, which were associated with better cardiac functional outcomes in females. We aimed to investigate the early, sex-specific functional and proteomic changes following myocardial ischemia in an unbiased approach.

methodsIschemia was induced in male (M-Isch) and female (F-Isch) rats with sc. injection of isoproterenol (85 mg/kg) daily for 2 days, while controls (M-Co, F-Co) received sc. saline solution. At 48 h after the first injection pressure-volume analysis was carried out to assess left ventricular function. FFPE tissue slides were scanned and analyzed digitally, while myocardial proteins were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using isobaric labeling. Concentrations of circulating steroid hormones were measured with LC-MS/MS. Feature selection (PLS and PLS-DA) was used to examine associations among functional, proteomic and hormonal datasets.

resultsInduction of ischemia resulted in 38% vs 17% mortality in M-Isch and F-Isch respectively. The extent of ischemic damage to surviving rats was comparable between the sexes. Systolic dysfunction was more pronounced in males, while females developed a more severe impairment of diastolic function. 2224 proteins were quantified, with 520 showing sex-specific differential regulation. Our analysis identified transcriptional, cytoskeletal, contractile, and mitochondrial proteins, molecular chaperones and the extracellular matrix as sources of disparity between the sexes. Bioinformatics highlighted possible associations of estrogens and their metabolites with early functional and proteomic alterations.

conclusionsOur study has highlighted sex-specific alterations in systolic and diastolic function shortly after ischemia, and provided a comprehensive look at the underlying proteomic changes and the influence of estrogens and their metabolites. According to our bioinformatic analysis, inflammatory, mitochondrial, chaperone, cytoskeletal, extracellular and matricellular proteins are major sources of intersex disparity, and may be promising targets for early sex-specific pharmacologic interventions.

Indexed as

Myocardial IschemiaProteomicsAnimalsChromatography, LiquidFemaleHeartHumansMaleRatsTandem Mass SpectrometryEstrogensLeft ventricular functionMyocardial ischemiaProteomic changesSex differences

Identifiers

PMID34895263
PMCPMC8666068
OpenAlexW4200043589

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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.