Columbia Researchers Uncover Dangerous Connection Between Serotonin and Heart Valve Disease - SciTechDaily

Serotonin tin interaction the mitral valve of the bosom and perchance accelerate a cardiac information known arsenic degenerative mitral regurgitation, according to a caller survey led by researchers astatine Columbia University’s Department of Surgery successful collaboration with the Pediatric Heart Valve Center astatine Children’s Hospital of Philadelphia (CHOP), the University of Pennsylvania, and the Valley Hospital Heart Institute. 

The results of the multicenter study, which was supported by a assistance from the National Heart, Lung, and Blood Institute and co-led by Columbia’s Giovanni Ferrari, PhD, and CHOP’s Robert J. Levy, MD, were published earlier this period successful Science Translational Medicine.

Degenerative Mitral Regurgitation

Degenerative mitral regurgitation (DMR) is 1 of the astir communal types of bosom valve disease. The mitral valve is located betwixt the near atrium and near ventricle of the heart. It closes tightly erstwhile the bosom contracts to forestall humor from leaking backmost into the near atrium.

In DMR, the signifier of the mitral valve becomes distorted, preventing the valve from closing completely. This allows humor to leak backmost toward the lungs (regurgitation), limiting the magnitude of oxygen-rich humor moving done the bosom to the remainder of the body.

As a result, DMR tin bring astir symptoms similar fatigue and shortness of breath. Because of the reduced ratio successful circulation, the bosom has to enactment harder, which implicit clip causes imperishable damage. This tin pb to a fig of superior and life-threatening cardiac issues, including atrial fibrillation and bosom failure.

Currently, determination is nary attraction for mitral valve degeneration. “Certain medications tin easiness the symptoms and forestall complications, but they bash not dainty the mitral valve,” says Ferrari, technological manager of the Cardiothoracic Research Program astatine Columbia. “If the degeneration of the mitral valve becomes severe, country to repair oregon regenerate the valve is needed.”

The Role of Serotonin

Serotonin plays a portion successful a wide scope of assemblage functions, including affectional state, digestion, sleep, memory, and humor clotting. Serotonin’s relation arsenic a neurotransmitter helps your encephalon modulate mood; little levels of serotonin are associated with anxiousness and depression.

Serotonin binds to circumstantial receptors connected the aboveground of a cell, sending a awesome to the compartment to enactment accordingly. A macromolecule known arsenic the serotonin transporter (SERT oregon 5-HTT) moves serotonin into the compartment to beryllium reabsorbed and recycled, a process known arsenic serotonin reuptake.

Medications called selective serotonin reuptake inhibitors (SSRIs) hindrance to the SERT to trim serotonin reuptake, allowing serotonin to stay disposable for longer periods. This accrued serotonin availability tin assistance amended symptoms of temper disorders. SSRIs are immoderate of the astir wide prescribed types of antidepressants and see well-known medications similar fluoxetine (Prozac) and sertraline (Zoloft).

Study Design

The survey examined objective information from much than 9,000 patients who had undergone valve repair oregon replacement country for DMR and evaluated 100 mitral valve biopsies. “Studying the information of these patients, we recovered that taking SSRIs was associated with terrible mitral regurgitation that needed to beryllium treated with country astatine a younger property than for patients not taking SSRIs,” says Ferrari.

The researchers besides studied successful vivo rodent models utilizing transgenic mice lacking the SERT cistron and mean mice. They discovered that mice without a SERT cistron developed thicker mitral valves and that mean mice treated with precocious doses of SSRIs besides developed thickened mitral valves.

Using familial analysis, the researchers identified familial variants successful the SERT cistron portion 5-HTTLPR that impact SERT activity. They recovered that a “long” variant of 5-HTTLPR makes SERT little progressive successful the mitral valve cells, particularly erstwhile determination are 2 copies (one maternal and 1 paternal). DMR patients with the “long-long” variant needed mitral valve country much often than those with different variants.

Mitral valve cells from DMR patients with the “long-long” variant were much prone to respond to serotonin by producing much collagen, changing the signifier of the mitral valve. Additionally, mitral valve cells with the “long-long” variant of 5-HTTLPR were much delicate to fluoxetine than those with different variants.

Implications for Patients with Mitral Valve Disease

The survey indicates that for DMR patients with the “long-long” variant, taking SSRIs lowers SERT enactment successful the mitral valve. The researchers suggest investigating DMR patients for imaginable debased SERT enactment by genotyping them for 5-HTTLPR, which tin beryllium determined easy from a DNA illustration obtained from the humor oregon a rima swab. “Assessing patients with DMR for debased SERT enactment whitethorn assistance place patients who whitethorn request mitral valve country earlier,” says Ferrari. “Promptly fixing a mitral valve that is precise leaky would support the bosom and could forestall congestive bosom failure.”

The researchers did not find a antagonistic effect with mean doses of SSRIs oregon the “long-long” variant successful cells from steadfast quality mitral valves. “A steadfast mitral valve tin astir apt basal debased SERT enactment without deforming,” says Ferrari. “It is improbable that debased SERT tin origin degeneration of the mitral valve by itself. SSRIs are mostly harmless for astir patients. Once the mitral valve has started to degenerate, it whitethorn beryllium much susceptible to serotonin and debased SERT.”

Additional probe whitethorn assistance find if DMR patients who respond good to SSRIs should beryllium regularly seen to measure progression of mitral degeneration, and whether DMR patients who are not responding good to SSRIs should see switching to a non-SSRI antidepressant alternatively than raising the dose of the SSRI.

Reference: “Decreased serotonin transporter enactment successful the mitral valve contributes to progression of degenerative mitral regurgitation” by Estibaliz Castillero, Emmett Fitzpatrick, Samuel J. Keeney, Alex M. D’Angelo, Benjamin B. Pressly, Michael T. Simpson, Mangesh Kurade, W. Clinton Erwin, Vivian Moreno, Chiara Camillo, Halley J. Shukla, Vaishali V. Inamdar, Arbi Aghali, Juan B. Grau, Elisa Salvati, Itzhak Nissim, Lubica Rauova, Mark A. Oyama, Stanley J. Stachelek, Chase Brown, Abba M. Krieger, Robert J. Levy and Giovanni Ferrari, 4 January 2023, Science Translational Medicine.
DOI: 10.1126/scitranslmed.adc9606