Common chemotherapy drug may lead to heart failure: Study
These immune responses are vital for heart maintenance, repair, and control of inflammation, according to the research published in the American Journal of Physiology-Heart and Circulatory Physiology.
This dysregulated immunometabolism impairs resolution of inflammation, and chronic, non-resolving inflammation leads to advanced heart failure.
Two key players in immunometabolism are immune-responsive enzymes called lipoxygenases and cyclooxygenases.
The researchers, led by Ganesh Halade, an assistant professor at UAB, used a mouse model to study the effect of doxorubicin on immunometabolism.
The drug also caused a wasting syndrome in the heart and the spleen, researchers said.
Mounting research has shown that the spleen - which acts as a reservoir of immune cells that speed to the site of heart injury to begin clearance of damaged tissue - plays a leading role in the initiation of the immune response after a heart attack.
Now, Halade and colleagues have found that the doxorubicin is also involved in the deleterious response to the spleen.
First, the researchers found that doxorubicin-induced irreversible dysregulation that lowered levels of lipoxygenases and cyclooxygenases in the left ventricle of the heart.
This reduced the levels of bioactive lipids mediators produced by these enzymes, mediators that usually would help resolve inflammation.
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