Duke-NUS scientists have made a significant breakthrough in the treatment of heart failure with preserved ejection fraction (HFpEF), a challenging form of heart disease. Their research revealed that heart cells affected by this condition exhibit elevated levels of glucagon, a hormone produced by the pancreas that increases blood sugar levels.
By blocking the activity of this hormone, researchers demonstrated notable improvements in heart function.
Heart failure is a growing global health crisis, with the heart’s ability to pump blood effectively compromised. In Singapore, it ranks as a leading cause of death, accounting for 17% of cardiac admissions.
Worldwide, approximately 64 million individuals are affected, with HFpEF representing about half of these cases.
In HFpEF, while the heart can pump normally, its muscles become too stiff to relax adequately and refill with blood. This condition is often found in older adults and those with risk factors such as high blood pressure, obesity, and diabetes.
Common symptoms include shortness of breath, fatigue, and decreased exercise capacity. This differs from heart failure with reduced ejection fraction (HFrEF), where the heart muscle weakens and fails to pump blood effectively.
Previous studies have examined how hypertension and metabolic diseases like diabetes stress the heart but have typically looked at these factors separately. The recent study published in Circulation Research fills this gap by considering both stressors and identifying the molecular pathways involved in HFpEF progression.
The research team, which included collaborators from several prestigious institutions such as the University of Cincinnati College of Medicine and the University of Toronto, explored how hypertension affects both lean and diabetic/obese hearts.
They found that lean models developed HFrEF, while obese models exhibited HFpEF. This discovery highlights how multiple stressors contribute to the disease and provides a valuable model for further investigation.
Using advanced single-cell RNA sequencing technology, researchers analyzed gene expression in individual heart cells, uncovering genetic variations linked to HFpEF. They found that glucagon-driven genes were particularly active in obese models.
Professor Wang Yibin, Director of the Cardiovascular & Metabolic Disorders Programme at Duke-NUS and senior author of the study, explained: “Under stress conditions like high blood pressure and metabolic disorders such as obesity and diabetes, glucagon signaling becomes overly active in heart cells. This increased activity leads to greater stiffness in the heart and impairs its ability to relax and fill with blood.”
The team tested a drug that blocks the glucagon receptor in a pre-clinical model of HFpEF. The results showed significant improvements in heart function, including reduced stiffness, enhanced relaxation, better filling capacity, and overall improved performance.
Assistant Professor Chen Gao from the University of Cincinnati College of Medicine and the study’s first author stated: “Our study provides strong evidence that a glucagon receptor blocker could effectively treat HFpEF. Since this drug is already being tested for diabetes treatment, it could expedite relief for millions of heart patients.”
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, added: “With an aging population, we expect more patients to face multiple conditions like heart failure, diabetes, and hypertension.
Understanding how these illnesses interact is crucial for developing effective treatments.”
The researchers aim to collaborate with clinical partners to conduct trials testing the glucagon receptor blocker on humans with HFpEF. If successful, this treatment could significantly enhance the quality of life for millions affected by this complex condition.
Duke-NUS continues to be a leader in medical education and biomedical research, focusing on understanding common diseases like heart failure and developing innovative treatment strategies for improved patient outcomes both locally and globally.
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