Article Impact Level: HIGH Data Quality: STRONG Summary of Communications Biology, 8(1), 1–16. https://doi.org/10.1038/s42003-025-08291-6 Dr. Jaideep Singh et al.
Points
- A preclinical study reveals that the protein annexin-A1, or ANXA1, plays a crucial role in protecting the heart and blood vessels from damage caused by high blood pressure, particularly in females.
- Researchers discovered that the female sex hormone estrogen is responsible for increasing the levels of this protective ANXA1 protein, establishing a direct biological link between the two.
- In the absence of ANXA1, female mice with hypertension exhibited more severe adverse cardiac remodeling and impaired mitochondrial function, underscoring the protein’s importance in cellular energy regulation.
- This work addresses a historical gap in cardiovascular research, which has often overlooked the distinct physiological mechanisms and treatment responses that exist between male and female patients with hypertension.
- The findings provide a strong foundation for developing new therapeutic ANXA1 mimetics specifically designed to address the unique pathophysiology of hypertension and prevent heart failure in women.
Summary
A recent preclinical study examined the sex-specific role of annexin A1 (ANXA1) in blood pressure regulation. In angiotensin II-induced hypertensive mouse models, a deficiency of ANXA1 was found to exacerbate adverse aortic and cardiac structural remodeling, mitochondrial proteome dysregulation, and impaired mitochondrial function. These detrimental effects were observed to be more pronounced in female subjects, suggesting a female-specific protective mechanism involving ANXA1. The study did not provide numerical data such as confidence intervals or hazard ratios for these preclinical outcomes.
The investigation further elucidated a mechanistic link between estrogen and ANXA1. The researchers demonstrated that estrogen upregulates ANXA1 levels, which, in turn, modulate inflammatory and mitochondrial networks. This finding establishes an estrogen-ANXA1 axis as a critical pathway in mitigating inflammation and preventing the pathological remodeling associated with hypertension in females. The dysregulation of this axis, therefore, is a key driver of the increased cardiovascular damage observed in ANXA1-deficient females.
These findings highlight a significant gap in the understanding of female-specific cardiovascular pathophysiology and underscore the need for sex-specific therapeutic strategies. The study proposes that developing therapeutic ANXA1 mimetics could offer a targeted approach to address the unique features of hypertension in women. The researchers aim to translate these findings to human studies, investigating the estrogen-ANXA1 axis in patients and testing ANXA1-boosting therapies in preclinical models to prevent hypertensive heart damage.
Link to the article: https://www.nature.com/articles/s42003-025-08291-6
References Singh, J., Jackson, K. L., Fang, H., Tang, F. S., Gueguen, C., Parker, A. M., Chen, H., Nowell, C. J., Kiriazis, H., Salimova, E., Woodman, O. L., Ritchie, R. H., Head, G. A., Greening, D. W., & Qin, C. X. (2025). Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice. Communications Biology, 8(1), 1–16. https://doi.org/10.1038/s42003-025-08291-6
