Following a heart attack, the same cells of the immune system that help put damaged heart tissue back together can malfunction and actually exacerbate the process that leads to heart failure. Because of this complicated dual role, researchers set out to develop a treatment that only temporarily disables these cells.
"Our data suggests that targeting specific immune cell subsets at defined stages of disease may represent a better approach to therapeutic immunomodulation to improve heart failure,” said the scientists involved in a new study published in Circulation: Heart Failure. Because without immune cells altogether, an individual would be immunocompromised.
Tissue damage after a heart attack often goes through two major phases of inflammation. The first is beneficial, early acute inflammation that is responsible for cleaning out dead and dying cells and beginning the reparation process in the tissue damaged by a lack of oxygenated blood. However, if the acute stage does not end when it should, healing doesn’t begin and damaging, chronic inflammation ensues.
A specific type of activated T cells, called CD4+ cells, were discovered by University of Alabama at Birmingham scientists to be intricately involved in the phase two chronic inflammation following a heart attack, inflammation that can lead to heart failure and death.
Immune cells from the spleen, pro-inflammatory macrophages and dendritic cells, are also involved. Dendritic cells act as antigen-presenting cells for T cells, enabling them to trigger the immune response. With this background knowledge established, researchers wondered if this process occurring in the heart tissue could be responsible for injury following a heart attack.
During their new study, the University of Alabama at Birmingham researchers first experimentally-induced heart attacks in mouse models, and after four weeks, they removed CD4+ T cells from the mice by injecting antibodies against the T cells. Removing the T cells prevented the left ventricle from growing progressively and dangerously large, what can lead to heart failure.
Next, also using experimentally-induced heart attacks in mouse models, researchers took spleen CD4+ cells from the heart attack mice and injected them into naive recipient mice with no induced heart attack. These cells alone led to long-lasting scarring and progressive enlargement in the left ventricle in addition to other conditions that characterize heart failure.
Although still in the mouse model stage, the results from this study have promise for someday reaching the clinic because they provide a temporary option for inhibiting immune cells, which are helpful to a certain extent. This experimental approach gives immune cells the chance to be beneficial and prevents them from going overboard, making outcomes promising for the patient recovering from a heart attack.