Doxorubicin disrupts the immune system to cause heart toxicity
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IMAGE: This is Ganesh Halade. view more 

Credit: UAB

BIRMINGHAM, Ala. – Doxorubicin is a chemotherapy drug widely used in ovarian, bladder, lung, thyroid and stomach cancers, but it carries a harmful side effect. The drug causes a dose-dependent heart toxicity that can lead to congestive heart failure.

University of Alabama at Birmingham researchers now describe an important contributor to that heart pathology — disruption of the metabolism that controls immune responses in the spleen and heart. These immune responses are vital for heart maintenance, repair and control of inflammation. This dysregulated immunometabolism impairs resolution of inflammation, and chronic, non-resolving inflammation leads to advanced heart failure.

Immunometabolism is the study of how metabolism regulates immune cell function, and it is a recent and growing aspect of immunology. Two key players in immunometabolism are immune-responsive enzymes called lipoxygenases and cyclooxygenases. These immune-sensitive enzymes create a variety of bioactive lipid mediators that regulate immune cell responses.

The UAB researchers, led by Ganesh Halade, Ph.D., an assistant professor in the UAB Department of Medicine’s Division of Cardiovascular Disease, used a mouse model to study the effect of doxorubicin on immunometabolism. In the mice, doxorubicin induced fibrosis in the heart, increased the programmed

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