Cardiac GRK2 protein levels show sexual dimorphism during aging and are regulated by ovarian hormones

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dc.contributor.author Arcones, A.C.
dc.contributor.author Martínez-Cignoni, M.R.
dc.contributor.author Vila-Bedmar, R.
dc.contributor.author Yáñez, C.
dc.contributor.author Lladó, I.
dc.contributor.author Proenza, A.M.
dc.contributor.author Mayor, F.
dc.contributor.author Murga, C.
dc.date.accessioned 2025-01-23T12:54:54Z
dc.date.available 2025-01-23T12:54:54Z
dc.identifier.citation Arcones, A.C., Martínez-Cignoni, M.R., Vila-Bedmar, R., Yáñez, C., Lladó, I., Proenza, A.M., Mayor, F., Murga, C. (2021). Cardiac GRK2 protein levels show sexual dimorphism during aging and are regulated by ovarian hormones. Cells, 10(673)
dc.identifier.uri http://hdl.handle.net/11201/167868
dc.description.abstract [eng] Cardiovascular disease (CVD) risk shows a clear sexual dimorphism with age, with a lower incidence in young women compared to age-matched men. However, this protection is lost after menopause. We demonstrate that sex-biased sensitivity to the development of CVD with age runs in parallel with changes in G protein-coupled receptor kinase 2 (GRK2) protein levels in the murine heart and that mitochondrial fusion markers, related to mitochondrial functionality and cardiac health, inversely correlate with GRK2. Young female mice display lower amounts of cardiac GRK2 protein compared to age-matched males, whereas GRK2 is upregulated with age specifically in female hearts. Such an increase in GRK2 seems to be specific to the cardiac muscle since a different pattern is found in the skeletal muscles of aging females. Changes in the cardiac GRK2 protein do not seem to rely on transcriptional modulation since adrbk1 mRNA does not change with age and no differences are found between sexes. Global changes in proteasomal or autophagic machinery (known regulators of GRK2 dosage) do not seem to correlate with the observed GRK2 dynamics. Interestingly, cardiac GRK2 upregulation in aging females is recapitulated by ovariectomy and can be partially reversed by estrogen supplementation, while this does not occur in the skeletal muscle. Our data indicate an unforeseen role for ovarian hormones in the regulation of GRK2 protein levels in the cardiac muscle which correlates with the sex-dependent dynamics of CVD risk, and might have interesting therapeutic applications, particularly for post-menopausal women.
dc.format application/pdf
dc.publisher MDPI
dc.relation.isformatof https://doi.org/10.3390/cells10030673
dc.relation.ispartof Cells, 2021, vol. 10, num. 673
dc.rights Attribution 4.0 International
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.classification 577 - Bioquímica. Biologia molecular. Biofísica
dc.subject.classification 61 - Medicina
dc.subject.other 577 - Material bases of life. Biochemistry. Molecular biology. Biophysics
dc.subject.other 61 - Medical sciences
dc.title Cardiac GRK2 protein levels show sexual dimorphism during aging and are regulated by ovarian hormones
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion
dc.type Article
dc.date.updated 2025-01-23T12:54:54Z
dc.subject.keywords estrogens
dc.subject.keywords Cardiovascular disease
dc.subject.keywords G protein-coupled receptor kinase 2 (GRK2)
dc.subject.keywords mitochondria
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.identifier.doi https://doi.org/10.3390/cells10030673


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