FEBRUARY 2023

According to a new study at Columbia University, Serotonin can negatively impact the mitral valve and exacerbate a cardiac condition called degenerative mitral regurgitation (DMR). Normally, the left atrium receives oxygenated blood, it gets shuttled to the left ventricle, where it gets pumped to the rest of the body. However, in DMR, the mitral valve does not close properly, which causes backwards blood flow. As a result, there’s less oxygenated blood being pumped than there should be. This subsequently causes fatigue and shortness of breath since the body's tissues are not meeting their oxygen needs. The heart will then compensate for this by working harder, which eventually can cause serious damage and lead to life-threatening heart conditions like atrial fibrillation and heart failure. When DMR patients’ mitral valves deteriorate enough, surgery becomes required to repair or replace the valve. 

The researchers in this study evaluated DMR patients who had a repair or replacement surgery to determine why some patients had worse mitral regurgitation. A common factor they noticed was that the youngest DMR patients were all on Serotonin Uptake Inhibitors (SSRIs). This demonstrated there was an aspect of serotonin that caused these medications to exacerbate DMR. To further analyze the relationship between mitral valve sensitivity and Serotonin, the researchers compared normal mice versus mice that had limited serotonin transporter activity. It was shown that mice without serotonin transporter function developed thicker mitral valves. This also occurred in mice that were treated with the SSRI fluoxetine. Essentially in both mice, serotonin reuptake was inhibited, resulting in increased serotonin levels. This demonstrated that mitral valves can have increased sensitivity to serotonin, thus validating the trend that SSRIs exacerbated patients’ DMR. This explains why these patients required surgery at younger ages. 

They then asked why certain patients on SSRI’s didn’t require surgery earlier in life? Subsequently, genetic testing was done and they saw that genetic variability in the SERT gene contributed to mitral valve sensitivity to Serotonin. It was found that patients with the “long” variant in the SERT gene had weakened serotonin transport activity, causing diminished reuptake. This was especially prevalent in patients with two copies of the “long” variant (one from each of their parents). Subsequently, it was determined that these patients experienced worse mitral regurgitation, thus receiving surgery earlier in life than other DMR patients. The researchers confirmed this by exposing mitral valve cells from these patients to serotonin. They noticed increased collagen production that changed the mitral valve’s shape. This explained many of these patients’ oversensitivity to the SSRI fluoxetine. 

The conclusion of the study was that “long long” variant individuals on SSRIs had weakened serotonin transporter activity in the mitral valve. As a result, DMR patients should be genetically screened for this genotype. This can enable surgical intervention preventing major cardiac issues like congestive heart failure.

References: 

https://www.science.org/doi/10.1126/scitranslmed.adc9606 

https://www.sciencedaily.com/releases/2023/01/230129193418.htm