Related Experiment Video
Updated: Sep 16, 2025
Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions
Published on: March 8, 2019
Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in
Jaideep Singh1,2, Kristy L Jackson1,2, Haoyun Fang2,3
1Drug, Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Insights
Annexin-A1 (ANXA1) deficiency worsens hypertension-induced cardiovascular damage, particularly in females. Estrogen influences ANXA1, highlighting a potential therapeutic target for sex-specific hypertension treatments.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Molecular Medicine
Background:
- Cardiovascular disease (CVD) shows significant sex-based differences, with underlying mechanisms often under-explored.
- Annexin-A1 (ANXA1), a pro-resolving mediator, is crucial for inflammation resolution and tissue homeostasis in the cardiovascular system.
- Sex-specific roles of ANXA1 in blood pressure regulation are not well understood.
Purpose of the Study:
- To investigate the sex-specific role of ANXA1 in angiotensin II-induced hypertension.
- To elucidate the mechanisms by which ANXA1 influences cardiovascular remodeling and mitochondrial function.
- To explore the interplay between estrogen and ANXA1 in the context of hypertension.
Main Methods:
- Utilized preclinical models of hypertension induced by angiotensin II.
- Assessed aortic and cardiac structural remodeling.
- Analyzed mitochondrial proteome and function.
- Investigated the influence of estrogen on ANXA1 expression.
Main Results:
- ANXA1 deficiency exacerbated adverse aortic and cardiac remodeling in hypertensive models.
- These effects were more pronounced in female models.
- Estrogen was found to upregulate ANXA1 levels, influencing inflammatory and mitochondrial networks.
- ANXA1 deficiency led to mitochondrial proteome dysregulation and impaired mitochondrial function.
Conclusions:
- Estrogen-ANXA1 axis plays a critical role in modulating inflammation and preventing pathological cardiovascular remodeling.
- This study highlights female-specific alterations in cardiac and aortic tissues during hypertension.
- Findings provide a basis for developing ANXA1-based therapeutics targeting hypertension in females.
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.
