Preclinical study validates spleen’s crucial role in cardiac repair



Although we may survive without a spleen, evidence continues to mount that this abdominal organ plays a more valuable role in our physiological defenses than previously thought.

The spleen contains a host of immune cells and signaling molecules that can be quickly mobilized to respond whenever a major injury such as a heart attack or viral invasion occurs. “

Ganesh Halade, PhD, Associate Professor of Cardiovascular Sciences, University of South Florida Health (USF Health) Morsani College of Medicine

Dr Halade led a new preclinical study that analyzed the interactions of the lipid mediator sphingosine-1-phosphate (S1P) in the spleen and heart during the transition from acute heart failure to chronic heart failure. Researchers have discovered new heart repair mechanisms to help shed light on the spleen-heart coordination of physiological inflammation in a mouse model of heart failure.

The study was published online August 20 in the American Journal of Physiology – Heart and Circulation.

“Simply put, we have shown that the spleen and heart work together via S1P for cardiac repair,” said lead researcher Dr. Halade, a member of the USF Health Heart Institute. “Our study also suggests that early detection of low or zero levels of S1P after a heart attack and targeted activation of this bioactive lipid mediator may provide cardioprotective therapy for patients at high risk for heart failure.”

Dr Halade and his colleagues have defined links between fatty acids, dysfunctional control of inflammation and heart failure. His lab is focused on finding ways to prevent, delay, or treat unresolved inflammation after a heart attack. In this latest study, the researchers turned their attention to where S1P is produced and its role in cardiac repair.

S1P is a deregulated lipid mediator during inflammatory responses, including heart failure. In addition, several groups have demonstrated the potential importance of this signaling molecule as a therapeutic target for heart failure triggered by heart attack and ischemia-reperfusion injury.

The USF Health study captured the time-dependent movement of S1P from the spleen through blood plasma flowing to the heart. The work was the first to quantify the interactions between S1P and the S1P 1 receptor (S1PR1) during the progression of acute to chronic heart failure, said Dr Halade.

The researchers defined S1P / S1PR1 signaling in mice and humans with heart failure after a heart attack. The otherwise young and healthy “safe” mice did not exhibit any variable cardiovascular risk factors such as obesity, diabetes, hypertension, and aging commonly seen in clinical settings. The researchers correlated the physiological data from the experiments on the mouse model of cardiac repair with what they observed in pathologically failing human hearts.

Among their main conclusions:

  • Heart-specific S1P and S1PR1 levels were reduced in patients with ischemic heart failure.
  • In safe mice, physiological cardiac repair was facilitated by activation of S1P in the heart and spleen. S1P / S1PR1 signaling increased in both organs from acute heart failure to chronic heart failure, helping to promote heart repair after a heart attack.
  • An increase in plasma S1P indicates cardiac repair in the acute phase of heart failure.
  • Selective activation of the S1P receptor in macrophages (immune cells that help clear inflammation and guide tissue repair) suppressed inflammation biomarkers and accelerated cardiac healing biomarkers in mouse cells.

“This study provides another example that the spleen should not be underestimated, as it contributes to the foundation of our immune health as well as the root cause of inflammatory diseases, including cardiovascular disease,” said Dr Halade. .


University of South Florida (USF Health)

Journal reference:

Gowda, SGB, et al. (2021) Sphingosine-1-phosphate interactions in the spleen and heart reflect the extent of cardiac repair in failed mice and human hearts. American Journal of Physiology-Cardiac and Circulatory Physiology.


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