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Sexual dimorphism in cardiac remodeling: the molecular mechanisms ruled by sex hormones in the heart

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Abstract

Heart failure (HF) is growing in prevalence, due to an increase in aging and comorbidities. Heart failure with reduced ejection fraction (HFrEF) is more common in men, whereas heart failure with preserved ejection fraction (HFpEF) has a higher prevalence in women. However, the reasons for these epidemiological trends are not clear yet. Since HFpEF affects mostly postmenopausal women, sex hormones should play a pivotal role in HFpEF development. Furthermore, for HFpEF, contrary to HFrEF, effective therapeutic approaches are missing. Interestingly, studies evidenced that some therapies can have better results in women than in HFpEF men, emphasizing the necessity of understanding these observations at a molecular level. Thus, herein, we review the molecular mechanisms of estrogen and androgen actions in the heart in physiological conditions and explain how its dysregulation can lead to disease development. This clarification is essential in the road for an effective personalized management of HF, particularly HFpEF, towards the development of sex-specific therapeutic approaches.

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Funding

This work was supported by Portuguese Foundation for Science and Technology (FCT), European Union, QREN, FEDER and COMPETE for funding the LAQV-REQUIMTE (UIDB/50006/2020), UnIC (UIDB/IC/00051/2020 and UIDP/00051/2020), and UMIB (UIDB/00215/2020 and UIDP/00215/2020) research units and the research projects DOCnet (NORTE-01–0145-FEDER-000003), NETDIAMOND (POCI-01–0145-FEDER-016385), and EXIT-HF (POCI-01–0145-FEDER-030011).

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Authors and Affiliations

  1. LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal

    Cláudia Ferreira, Rita Ferreira & Francisco Amado

  2. Department of Surgery and Physiology, Cardiovascular R&D Center (UnIC), Faculty of Medicine, University of Porto, Porto, Portugal

    Fábio Trindade, João Sérgio Neves, Adelino Leite-Moreira & Rita Nogueira-Ferreira

  3. Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário São João, Porto, Portugal

    João Sérgio Neves

  4. Department of Cardiothoracic Surgery, Centro Hospitalar Universitário São João, Porto, Portugal

    Adelino Leite-Moreira

  5. Department of Cardiology, Hospital Santo António, Centro Hospitalar Universitário do Porto, Porto, Portugal

    Mário Santos

  6. UMIB - Unidade Multidisciplinar de Investigação Biomédica, ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

    Mário Santos & Rita Nogueira-Ferreira

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  1. Cláudia Ferreira
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  2. Fábio Trindade
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  8. Rita Nogueira-Ferreira
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Contributions

R.N.F., M.S., F.A., R.F., and C.F. had the idea for the article; R.N.F., F.T., J.S.N., and C.F. performed the literature search; R.N.F., F.T., and C.F. drafted the manuscript; and M.S., F.A., A.L.M., and R.F. critically revised the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Rita Nogueira-Ferreira.

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Ferreira, C., Trindade, F., Ferreira, R. et al. Sexual dimorphism in cardiac remodeling: the molecular mechanisms ruled by sex hormones in the heart. J Mol Med 100, 245–267 (2022). https://doi.org/10.1007/s00109-021-02169-w

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