Columbia Study Links Serotonin Signaling to Mitral Valve Disease Progression

A Small Heart Valve With a Critical Role

The mitral valve sits between the heart’s left atrium and left ventricle. The left atrium receives oxygen-rich blood returning from the lungs, while the left ventricle pumps that blood throughout the body. Each time the heart contracts, the mitral valve should close firmly. It functions like a one-way gate, keeping blood from flowing backward into the upper chamber. In DMR, one of the most common forms of heart valve disease, the valve tissue degenerates. The thin flaps that should meet neatly can thicken, stretch, or lose their normal shape. Consequently, the valve can no longer seal completely, allowing blood to leak backward into the left atrium, a process known as regurgitation.

This leak can raise pressure toward the lungs while reducing the amount of oxygen-rich blood that moves forward through the heart. Some people have no noticeable symptoms at first. As the condition progresses, however, fatigue and shortness of breath can develop. The heart must also work harder to maintain circulation. Over time, that added strain can permanently damage the heart and contribute to serious, life-threatening conditions such as atrial fibrillation—an irregular heart rhythm—and heart failure, which means the heart cannot pump enough blood to meet the body’s needs.

A Multicenter Investigation

The research was led by the Department of Surgery at Columbia University in collaboration with the Pediatric Heart Valve Center at the Children’s Hospital of Philadelphia (CHOP), the University of Pennsylvania, and the Valley Hospital Heart Institute. Levy, MD.

Subtle changes in a key molecular pathway may play a larger role in valve disease than previously thought, offering clues for future diagnosis and treatment. Serotonin is best known for its role in mood, sleep, digestion, memory, and blood clotting, but new research suggests it may also influence how certain heart valve diseases progress. It works by binding to receptors on the surface of a cell, triggering specific responses. Afterward, a protein known as the serotonin transporter (SERT or 5-HTT) helps regulate these levels by pulling serotonin back into cells.

Limitations of Current Treatments

Currently, there is no medication that can reverse the underlying valve damage associated with DMR. While medicines can ease symptoms and help manage complications, they cannot address the structural degeneration of the valve itself.

“Certain medications can ease the symptoms and prevent complications, but they do not treat the mitral valve,” says Giovanni Ferrari, scientific director of the Cardiothoracic Research Program at Columbia. “If the degeneration of the mitral valve becomes severe, surgery to repair or replace the valve is needed.”

Laboratory and Biological Findings

To investigate the impact of serotonin on the heart, researchers studied mice that lacked the serotonin transporter (SERT) gene. When these mice were compared to normal mice, the SERT knockout mice exhibited a thickened mitral valve. To visualize this, the valves were stained with prico-sirius red to highlight the presence of collagen. These findings reveal a potential connection between serotonin activity and the progression of a widespread heart valve disorder, suggesting that the chemical messenger may influence the structural remodeling of valve tissue.

The research underscores that while serotonin’s role as a neurotransmitter helps the brain regulate mood, lower levels of serotonin are associated with anxiety and depression. By exploring these molecular pathways, the multicenter team has provided new insights into a condition that affects millions of people worldwide, particularly older adults, and remains a significant focus of cardiovascular surgery and research.

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