Common cause of heart failure may be different in men and women

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A new study from the UC Davis School of Medicine has revealed significant cellular differences between male and female mice with heart failure with preserved ejection fraction (HFpEF), potentially paving the way for gender-specific treatments for this condition in humans.

HFpEF, a type of heart failure, occurs when the heart muscle contracts normally but doesn’t relax properly between beats, which is essential for the heart to fill properly with blood.

This condition, also known as diastolic dysfunction, can be due to the heart being overly stiff or the contraction process lingering too long.

The study, which appeared in Cardiovascular Research, indicates that these dysfunctions manifest differently in male and female mice.

In females, the issue stems from altered heart filament proteins, specifically a change in the proteins titin and troponin I, which make the heart muscle cells functionally stiffer.

In contrast, male mice exhibited slowed calcium removal from their heart cells, which hinders the heart’s ability to relax fully between beats.

Donald M. Bers, chair of the Department of Pharmacology and a senior author of the study, emphasized the importance of this discovery.

He highlighted that if similar biological differences are found in humans, treatment strategies for HFpEF might need to be tailored by gender. Currently, HFpEF affects nearly half of all heart failure patients, with a notably higher prevalence in women than in men.

The research used an innovative “two-hit” mouse model to study the disease.

This model involved mice genetically modified to lack a leptin receptor, leading them to become obese and diabetic, coupled with an infusion of aldosterone, which causes fluid retention. This setup mimics common conditions in many HFpEF patients.

Key findings from this model showed that male mice also displayed more abnormal heart rhythms, known as arrhythmias, which are less common in the female mice.

These insights into how each gender responds at the cellular level to the same heart conditions could lead to more effective, targeted treatments.

Bence Hegyi, an associate project scientist in the Bers Lab and co-senior author, noted the potential for future clinical trials with sex-specific drugs.

For women, treatments could focus on reducing cardiac stiffness, whereas for men, enhancing calcium removal might be more beneficial.

Despite the promising findings, the researchers caution that the study’s mouse model may not represent all human cases of HFpEF, as the model primarily reflects patients who are significantly obese and diabetic.

Further studies, both preclinical and clinical, are needed to explore the applicability of these results across different subpopulations of HFpEF patients and to confirm the potential benefits of sex-specific treatments.

This study not only highlights the nuanced nature of heart failure but also underscores the critical need for personalized medicine in treating complex diseases like HFpEF.

If you care about heart failure, please read studies about diabetes drug that could revolutionize heart failure treatment, and this drug can be a low-cost heart failure treatment

For more information about heart health, please see recent studies that exercise in middle age reversed worrisome heart failure, and results showing this drug combo can cut risk of stroke and heart attack by half.

The research findings can be found in Cardiovascular Research.

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