Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice
Abstract Background Sex and age have substantial influence on thyroid function. Sex influences the risk and clinical expression of thyroid disorders (TDs), with age a proposed trigger for the development of TDs. Cardiac function is affected by thyroid hormone levels with gender differences. Accordin...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Proteome Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12953-020-00167-3 |
| _version_ | 1818323371170988032 |
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| author | Wei Zhong Zhu Aaron Olson Michael Portman Dolena Ledee |
| author_facet | Wei Zhong Zhu Aaron Olson Michael Portman Dolena Ledee |
| author_sort | Wei Zhong Zhu |
| collection | DOAJ |
| description | Abstract Background Sex and age have substantial influence on thyroid function. Sex influences the risk and clinical expression of thyroid disorders (TDs), with age a proposed trigger for the development of TDs. Cardiac function is affected by thyroid hormone levels with gender differences. Accordingly, we investigated the proteomic changes involved in sex based cardiac responses to thyroid dysfunction in elderly mice. Methods Aged (18–20 months) male and female C57BL/6 mice were fed diets to create euthyroid, hypothyroid, or hyperthyroid states. Serial echocardiographs were performed to assess heart function. Proteomic changes in cardiac protein profiles were assessed by 2-D DIGE and LC-MS/MS, and a subset confirmed by immunoblotting. Results Serial echocardiographs showed ventricular function remained unchanged regardless of treatment. Heart rate and size increased (hyperthyroid) or decreased (hypothyroid) independent of sex. Pairwise comparison between the six groups identified 55 proteins (≥ 1.5-fold difference and p < 0.1). Compared to same-sex controls 26/55 protein changes were in the female hypothyroid heart, whereas 15/55 protein changes were identified in the male hypothyroid, and male and female hyperthyroid heart. The proteins mapped to oxidative phosphorylation, tissue remodeling and inflammatory response pathways. Conclusion We identified both predicted and novel proteins with gender specific differential expression in response to thyroid hormone status, providing a catalogue of proteins associated with thyroid dysfunction. Pursuit of these proteins and their involvement in cardiac function will expand our understanding of mechanisms involved in sex-based cardiac response to thyroid dysfunction. |
| first_indexed | 2024-12-13T11:11:37Z |
| format | Article |
| id | doaj.art-d911726f14f54308870e4253228729b1 |
| institution | Directory Open Access Journal |
| issn | 1477-5956 |
| language | English |
| last_indexed | 2024-12-13T11:11:37Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Proteome Science |
| spelling | doaj.art-d911726f14f54308870e4253228729b12022-12-21T23:48:44ZengBMCProteome Science1477-59562020-12-0118111310.1186/s12953-020-00167-3Sex impacts cardiac function and the proteome response to thyroid hormone in aged miceWei Zhong Zhu0Aaron Olson1Michael Portman2Dolena Ledee3Center for Integrative Brain Research, Seattle Children’s Research InstituteCenter for Integrative Brain Research, Seattle Children’s Research InstituteCenter for Integrative Brain Research, Seattle Children’s Research InstituteCenter for Integrative Brain Research, Seattle Children’s Research InstituteAbstract Background Sex and age have substantial influence on thyroid function. Sex influences the risk and clinical expression of thyroid disorders (TDs), with age a proposed trigger for the development of TDs. Cardiac function is affected by thyroid hormone levels with gender differences. Accordingly, we investigated the proteomic changes involved in sex based cardiac responses to thyroid dysfunction in elderly mice. Methods Aged (18–20 months) male and female C57BL/6 mice were fed diets to create euthyroid, hypothyroid, or hyperthyroid states. Serial echocardiographs were performed to assess heart function. Proteomic changes in cardiac protein profiles were assessed by 2-D DIGE and LC-MS/MS, and a subset confirmed by immunoblotting. Results Serial echocardiographs showed ventricular function remained unchanged regardless of treatment. Heart rate and size increased (hyperthyroid) or decreased (hypothyroid) independent of sex. Pairwise comparison between the six groups identified 55 proteins (≥ 1.5-fold difference and p < 0.1). Compared to same-sex controls 26/55 protein changes were in the female hypothyroid heart, whereas 15/55 protein changes were identified in the male hypothyroid, and male and female hyperthyroid heart. The proteins mapped to oxidative phosphorylation, tissue remodeling and inflammatory response pathways. Conclusion We identified both predicted and novel proteins with gender specific differential expression in response to thyroid hormone status, providing a catalogue of proteins associated with thyroid dysfunction. Pursuit of these proteins and their involvement in cardiac function will expand our understanding of mechanisms involved in sex-based cardiac response to thyroid dysfunction.https://doi.org/10.1186/s12953-020-00167-3Thyroid hormoneHeartAgedProteomicsSex-based |
| spellingShingle | Wei Zhong Zhu Aaron Olson Michael Portman Dolena Ledee Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice Proteome Science Thyroid hormone Heart Aged Proteomics Sex-based |
| title | Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice |
| title_full | Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice |
| title_fullStr | Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice |
| title_full_unstemmed | Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice |
| title_short | Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice |
| title_sort | sex impacts cardiac function and the proteome response to thyroid hormone in aged mice |
| topic | Thyroid hormone Heart Aged Proteomics Sex-based |
| url | https://doi.org/10.1186/s12953-020-00167-3 |
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