Columbia researchers find link between seroto

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Image: This image shows the mitral valve of a mouse heart lacking the serotonin transporter (SERT) gene. Valves were stained with plicosirius red to show collagen. SERT knockout mice had thicker mitral valves compared to normal mice.
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Credit: Columbia University Irving Medical Center

Serotonin affects the heart’s mitral valves and can accelerate a heart condition known as degenerative mitral regurgitation, one researcher said. new research It is led by investigators from Columbia University Surgery in collaboration with the Children’s Hospital of Philadelphia (CHOP) Pediatric Heart Valve Center, the University of Pennsylvania, and the Valley Hospital Heart Institute.

Results of a multicenter study supported by a grant from the National Heart, Lung, and Blood Institute and co-led by Columbia University Dr. Giovanni Ferrariand Robert J. Levy, MD of CHOP recently Science Translational Medicine.

Regressive mitral regurgitation

Degenerative mitral regurgitation (DMR) is one of the most common types. valvular heart diseaseThe mitral valve is located between the left atrium and left ventricle of the heart. When the heart contracts, it closes tightly to prevent blood from flowing back into the left atrium.

DMR distorts the shape of the mitral valve and prevents it from closing completely. This causes blood to flow backwards (regurgitation) towards the lungs, limiting the amount of oxygen-rich blood that moves through the heart to the rest of the body.

As a result, DMR can cause symptoms such as fatigue and shortness of breath. Because circulation is less efficient, the heart has to work harder, causing permanent damage over time. can cause it.

There is currently no cure for mitral valve degeneration. “Certain drugs can relieve symptoms and prevent complications, but they don’t treat the mitral valve,” says Ferrari, scientific director of Columbia’s Cardiothoracic Research Program. When degeneration becomes severe, surgery to repair or replace you need a valve. “

Role of serotonin

Serotonin is involved in many bodily functions, including emotional states, digestion, sleep, memory, and blood clotting. Serotonin’s role as a neurotransmitter helps the brain regulate mood. Low levels of serotonin are associated with anxiety and depression.

Serotonin binds to specific receptors on the surface of cells, signaling cells to act accordingly. A protein known as the serotonin transporter (SERT or 5-HTT) moves serotonin into the cell for reuptake and reuse. This process is known as serotonin reuptake.

Drugs called selective serotonin reuptake inhibitors (SSRIs) bind to SERT and reduce serotonin reuptake, making it available for longer. This increased serotonin availability helps improve symptoms of mood disorders. ), including well-known drugs such as

research design

This study examined clinical data from over 9,000 patients undergoing valve repair or replacement surgery for DMR and evaluated 100 mitral valve biopsies. “A study of these patient data showed that patients taking SSRIs were associated with severe mitral regurgitation requiring surgery at a younger age than those not taking SSRIs. I know there is,” says Ferrari.

The researchers also studied an in vivo mouse model using transgenic mice lacking the SERT gene and normal mice. They found that mice lacking the SERT gene developed thicker mitral valves, and normal mice treated with high doses of SSRIs also developed thickened mitral valves.

Using genetic analysis, researchers identified a genetic variant in the SERT gene region 5-HTTLPR that affects SERT activity. They found that a ‘long’ variant of 5-HTTLPR reduced her SERT activity in mitral valve cells. This is especially noticeable when he has two copies (one maternal and one paternal). DMR patients with the “long-long” variant required mitral valve surgery more frequently than those with other variants.

Mitral valve cells from DMR patients with the “long-long” variant tended to respond to serotonin by altering mitral valve shape and producing more collagen. Mitral valve cells with the ‘long-long’ variant of were more sensitive to fluoxetine than those with other variants.

Effects on patients with mitral valve disease

This study shows that in patients with DMR who have the “long-long” variant, taking SSRIs reduces SERT activity in the mitral valve. The researchers propose to test whether a DMR patient may have low SERT activity by examining her 5-HTTLPR genotype. This can easily be determined from DNA samples obtained from blood or buccal swabs. “Evaluating DMR patients with low SERT activity may help identify early those patients who need mitral valve surgery,” says Ferrari. By repairing the heart, it can protect the heart and prevent congestive heart failure.

The researchers found no adverse effects from normal doses of SSRIs or the ‘long-long’ variant in healthy human mitral valve cells. “A healthy mitral valve can probably withstand his low SERT activity without deformity,” says Ferrari. “Low SERT is unlikely to cause degeneration of the mitral valve itself. SSRIs are generally safe for most patients. I have.”

Additional studies are investigating whether patients with DMR who are good responders to SSRIs need to be seen regularly to assess the progression of mitral valve degeneration, and whether patients with DMR who are poor responders to SSRIs need to be seen at lower doses of SSRIs. It may help determine whether switching to a non-SSRI antidepressant should be considered instead of increasing. SSRIs.

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