Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice
Abstract Cardiovascular disease exhibits distinct sex-based differences, yet the mechanisms underlying these differences remain under-explored. The pro-resolving mediator annexin-A1 (ANXA1) is a pivotal regulator in inflammation resolution and tissue homeostasis, including within the cardiovascular...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08291-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849238307850944512 |
|---|---|
| author | Jaideep Singh Kristy L. Jackson Haoyun Fang Feng Shii Tang Cindy Gueguen Alex M. Parker HsinErh Chen Cameron J. Nowell Helen Kiriazis Ekaterina Salimova Owen L. Woodman Rebecca H. Ritchie Geoffrey A. Head David W. Greening Cheng Xue Qin |
| author_facet | Jaideep Singh Kristy L. Jackson Haoyun Fang Feng Shii Tang Cindy Gueguen Alex M. Parker HsinErh Chen Cameron J. Nowell Helen Kiriazis Ekaterina Salimova Owen L. Woodman Rebecca H. Ritchie Geoffrey A. Head David W. Greening Cheng Xue Qin |
| author_sort | Jaideep Singh |
| collection | DOAJ |
| description | Abstract Cardiovascular disease exhibits distinct sex-based differences, yet the mechanisms underlying these differences remain under-explored. The pro-resolving mediator annexin-A1 (ANXA1) is a pivotal regulator in inflammation resolution and tissue homeostasis, including within the cardiovascular system. However, the sex-specific differences in ANXA1 in blood pressure regulation have not been investigated. Here, we demonstrate that deficiency of ANXA1 exacerbates angiotensin II-induced adverse aortic and cardiac structural remodeling, mitochondrial proteome dysregulation, and impaired mitochondrial function in preclinical hypertensive models, exacerbated in females. Mechanistically, we demonstrate that estrogen upregulates ANXA1 levels, associated with dysregulation of inflammatory and mitochondrial networks, suggesting that the estrogen-ANXA1 axis plays a critical role in modulating inflammation and preventing pathological remodeling. In conclusion, this study advances the understanding of female-specific cardiac and aortic tissue and cellular alterations in hypertension, providing a platform for developing therapeutic ANXA1 mimetics that address the unique pathophysiological features of hypertension in females. |
| format | Article |
| id | doaj-art-7bab199dba18426fab9f206df8dcff13 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-7bab199dba18426fab9f206df8dcff132025-08-20T04:01:41ZengNature PortfolioCommunications Biology2399-36422025-07-018111610.1038/s42003-025-08291-6Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in miceJaideep Singh0Kristy L. Jackson1Haoyun Fang2Feng Shii Tang3Cindy Gueguen4Alex M. Parker5HsinErh Chen6Cameron J. Nowell7Helen Kiriazis8Ekaterina Salimova9Owen L. Woodman10Rebecca H. Ritchie11Geoffrey A. Head12David W. Greening13Cheng Xue Qin14Drug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityDrug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityBaker Heart & Diabetes InstituteDrug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityBaker Heart & Diabetes InstituteDrug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityDrug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityDrug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityBaker Heart & Diabetes InstituteMonash Biomedical Imaging, Monash University, ClaytonDrug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityDrug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityBaker Heart & Diabetes InstituteBaker Heart & Diabetes InstituteDrug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityAbstract Cardiovascular disease exhibits distinct sex-based differences, yet the mechanisms underlying these differences remain under-explored. The pro-resolving mediator annexin-A1 (ANXA1) is a pivotal regulator in inflammation resolution and tissue homeostasis, including within the cardiovascular system. However, the sex-specific differences in ANXA1 in blood pressure regulation have not been investigated. Here, we demonstrate that deficiency of ANXA1 exacerbates angiotensin II-induced adverse aortic and cardiac structural remodeling, mitochondrial proteome dysregulation, and impaired mitochondrial function in preclinical hypertensive models, exacerbated in females. Mechanistically, we demonstrate that estrogen upregulates ANXA1 levels, associated with dysregulation of inflammatory and mitochondrial networks, suggesting that the estrogen-ANXA1 axis plays a critical role in modulating inflammation and preventing pathological remodeling. In conclusion, this study advances the understanding of female-specific cardiac and aortic tissue and cellular alterations in hypertension, providing a platform for developing therapeutic ANXA1 mimetics that address the unique pathophysiological features of hypertension in females.https://doi.org/10.1038/s42003-025-08291-6 |
| spellingShingle | Jaideep Singh Kristy L. Jackson Haoyun Fang Feng Shii Tang Cindy Gueguen Alex M. Parker HsinErh Chen Cameron J. Nowell Helen Kiriazis Ekaterina Salimova Owen L. Woodman Rebecca H. Ritchie Geoffrey A. Head David W. Greening Cheng Xue Qin Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice Communications Biology |
| title | Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice |
| title_full | Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice |
| title_fullStr | Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice |
| title_full_unstemmed | Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice |
| title_short | Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice |
| title_sort | annexin a1 deficiency uncovers female specific pathways in blood pressure control and cardiovascular remodeling in mice |
| url | https://doi.org/10.1038/s42003-025-08291-6 |
| work_keys_str_mv | AT jaideepsingh annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT kristyljackson annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT haoyunfang annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT fengshiitang annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT cindygueguen annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT alexmparker annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT hsinerhchen annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT cameronjnowell annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT helenkiriazis annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT ekaterinasalimova annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT owenlwoodman annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT rebeccahritchie annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT geoffreyahead annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT davidwgreening annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice AT chengxueqin annexina1deficiencyuncoversfemalespecificpathwaysinbloodpressurecontrolandcardiovascularremodelinginmice |