Link between oestrogen and heart health found in women

A new preclinical study has revealed the role of the female sex hormone oestrogen in protecting the hearts of women with high blood pressure — a link that has not previously been fully understood by scientists.

The study, led by the Monash Institute of Pharmaceutical Sciences (MIPS) and published in the journal Communications Biology, identified that oestrogen increases the levels of a natural protein called ‘annexin-A1’ (ANXA1) in female mice. The MIPS team has previously shown that ANXA1 plays a critical role in regulating blood pressure.

In the current study, the researchers discovered that when ANXA1 is missing, high blood pressure leads to more severe damage in the heart and main blood vessels, especially in females. Their findings suggest that the oestrogen–ANXA1 association plays an important role in protecting women’s hearts from damage caused by high blood pressure, and could pave the way for new medicines that mimic ANXA1 and thus improve heart health in women.

“Essentially, we found that oestrogen helps increase ANXA1 protein, and when ANXA1 is missing, the heart is more vulnerable to damage due to poor mitochondrial function, the body’s energy system,” said first author Dr Jaideep Singh.

The research may explain why women may experience heart disease differently from men, especially when they have high blood pressure, with co-lead author Dr Chengxue Helena Qin stating, “There has been a major gap in understanding how high blood pressure and its treatments affect men and women differently. Clinical trials have historically overlooked sex-specific responses, leaving women underrepresented and underserved.”

Qin continued, “There’s an urgent need to uncover the distinct mechanisms driving hypertension and its cardiovascular complications in females — an underexplored population. Closing this knowledge gap is essential for developing more effective, sex-specific treatments.”

“We’re really excited about what this discovery could mean for future new treatments that enhance ANXA1, providing better protection for women with high blood pressure,” Singh added. “These therapies might help prevent serious problems like heart failure by focusing on the unique ways women’s hearts and blood vessels work. It also highlights the importance of doctors considering sex differences when deciding how to treat heart disease.”

Qin said the team’s goal is to move towards studying how oestrogen controls ANXA1 in humans to see if it works the same way as in animals — a process that will involve testing new medicines that boost ANXA1 in animal studies to check if these can protect the heart from damage caused by high blood pressure.

“Additionally, our team will investigate whether this protective system plays a role in other heart conditions that impact men and women differently,” she said.

Joint senior author Professor David Greening, Head of Molecular Proteomics at the Baker Heart and Diabetes Institute, said the study reveals the power of proteomics in advancing our understanding of the causes of heart and blood vessel diseases.

“It also provides detailed molecular insights into why men and women experience these conditions differently, helping us move toward more precise and targeted therapies for high blood pressure and related heart problems,” he said. Ultimately, the team aims to advance their findings towards clinical testing, particularly to benefit women with high blood pressure.

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