The spleen is one of the organs we can live without, but researchers are increasingly recognizing its importance. We know the spleen helps remove old cells from the blood, and it has an important role in the immune system by acting as a repository of cells and molecules that can be rapidly deployed when injury or infection occurs. Scientists have also been investigating the links between the spleen and the heart. Reporting in the American Journal of Physiology - Heart and Circulatory Physiology, new research has suggested that during heart failure, the spleen can help coordinate repair mechanisms.
A molecule called sphingosine-1-phosphate (S1P) is a lipid mediator that has a variety of signaling roles throughout the body. Research has indicated that S1P can become dysregulated during heart failure, and that it has potential as a therapeutic target. This study has elaborated on those findings.
“Simply put, we showed that the spleen and the heart work together through S1P for cardiac repair,” said study leader Ganesh Halade, Ph.D., an associate professor of cardiovascular sciences at the USF Health Morsani College of Medicine. The research also suggested that if post-heart attack S1P levels are monitored in patients and found to be low, it may be possible to help them recover if SP1 is targeted for activation, Halade added.
This approach could be useful in treating heart failure caused by heart attack or ischemia-reperfusion injury.
In this work, a mouse model was used to trace the movement of SP1 from the spleen to circulation, and then to the heart. It's the first to measure the interactions between SP1 and its receptor S1PR1 as acute heart failure progresses to a chronic condition, noted Halade. In mice, S1P/S1PR signaling increased in both the spleen and the heart during acute and chronic heart failure, which seemed to promote cardiac repair.
The study also indicated that S1P and S1PR1 levels in the heart are reduced in people with ischemic heart failure.
The researchers found that when the S1P receptor was activated in immune cells called macrophages, which play a role in inflammation, the levels of cardiac repair biomarkers increased, and inflammatory molecule levels were decreased.
“This study provides another example that the spleen should not be underestimated, because it contributes to the foundation of our immune health as well as the root cause of inflammatory diseases, including cardiovascular disease,” noted Halade.