Evidence mapPaperPMID 42174678Full record

ArticleBiology of sex differences2026

Sex differences in cardiac recovery and ventricular gene expression in a rat model of donation after circulatory death.

Anja Helmer, Alexia Clavier, Maria Arnold, Adrian Segiser, Heidi E L Lischer, Selianne Graf, Mojgan Masoodi, Georgia Beer, Rahel Ottersberg, Manuel Egle and 2 more

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Article in Biology of sex differences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Anja HelmerDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Alexia ClavierDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Maria ArnoldDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Adrian SegiserDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Heidi E L LischerInterfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.
Selianne GrafDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Mojgan MasoodiUniversity Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Georgia BeerDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Rahel OttersbergDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Manuel EgleDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Matthias SiepeDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Sarah LongnusDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. sarah.henninglongnus@insel.ch.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHeart donation after circulatory death (DCD) is a promising strategy to increase graft supply. However, in contrast to conventional heart transplantation, in which organs are retrieved from heart-beating donors, DCD hearts are subjected to damaging conditions before and during functional, warm in-situ ischemia in the donor, leading to ischemia-reperfusion injury (IRI). Although sex differences have been identified in other contexts of cardiac IRI, such as myocardial infarction, they remain underexplored in DCD. Therefore, we aimed to investigate whether sex differences induce changes in the expression of genes in response to cardiac DCD conditions, including IRI, which may contribute to sexual dimorphism in graft quality.

methods102 animals were included in this study. Male, female, and ovariectomized (OVX) Wistar rats underwent simulated DCD with no or 22 min of functional, warm in-situ ischemia, followed by oxygenated reperfusion with left-ventricular loading. Functional recovery was assessed and left-ventricular tissue was used for RNA-sequencing.

resultsRecovery of left ventricular function was decreased by functional, warm in-situ ischemia, but significantly better in females than in males, with OVX resembling the males. Reperfusion induced inflammatory, stress-response and metabolic-related pathways in all groups. Expression of 110 genes correlated with cardiac recovery, many of which were more abundant in females compared to males, consistent with a role in improved post-ischemic ventricular function. Among these genes, Igfbp3, Fam78b, and Galnt10 were differentially expressed in females compared to males and OVX, suggesting an influence of female sex hormones.

conclusionsCompared to male hearts, cardiac recovery is significantly higher in female hearts after exposure to DCD conditions and is accompanied by an increased expression of genes related to quality control programs that positively correlate with ventricular function. Significantly higher expression of genes related to energy metabolism, including fatty acid metabolism, and inflammatory pathways was revealed in males compared to females and is associated with decreased recovery. This study suggests potential new therapeutic targets for optimizing cardiac DCD graft quality, and highlights the importance of underlying sex and sex-hormone differences, e.g. in inflammatory pathways and metabolic adaptations, that should be taken into consideration for the implementation of sex-specific precision therapies.

Indexed as

Gene ExpressionHeart VentriclesSex CharacteristicsAnimalsFemaleHeart TransplantationMaleOvariectomyRatsRats, WistarVentricular Function, LeftBulk RNA Sequencing (RNA-Seq.)CardioprotectionDonation after circulatory death (DCD)Ex vivo/ex-situ heart perfusionHeart transplantationSex as a biological variable (SABV)Transcriptomics

Identifiers

PMID42174678
PMCPMC13386792

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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 Socratic graph.