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Treating Heart Failure by Preventing Early Macrophage Infiltration

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Researchers at the University of Alabama at Birmingham have discovered a potential target for therapies that may prevent or delay heart failure from pressure overload of the heart. It could also be a biomarker to warn physicians that a patient is at risk of this happening.

Early macrophage infiltration is a step in heart failure

In a new study, Dr. Sumanth Prabhu and his team showed that preventing the early infiltration of CCR2+ macrophages into the heart, in a mouse model of heart failure, significantly reduced enlargement of the heart and the decline of the pumping ability that leads to heart failure [1]. This means that the infiltration of macrophages is a critical step in heart failure.

The researchers used two approaches to prevent early macrophage infiltration; first, they used an inhibitor of the macrophage cell-surface CCR2 chemokine receptor, and second, an antibody that selectively removes CCR2+ macrophages. Migrating macrophages use the CCR2 receptor to locate damaged tissues, so blocking the receptor or removing the initial macrophages arriving at the injury site offers a potential therapeutic target.

It was already known that pressure-overload heart failure is linked to the inflammation produced by activated T cells at the injury site. The new study shows the association between the early infiltration of macrophages and the T cell response during pressure overload of the heart.



During the experiment, the researchers found that a week after inducing pressure load in the model mice, the heart showed an elevated expression of three chemokines that summon immune cells to an injury site and bind to the CCR2 receptor on macrophages.

They also observed an increased number of monocytes with the cell-surface markers Ly6C and CCR2 circulating in the bloodstream. Ultimately, this led to an eightfold increase in the number of CCR2+ macrophages infiltrating the heart. These CCR2+ macrophages are derived from the circulating monocytes.

The research team found that blocking the infiltration of macrophages to the heart also reduced the infiltration of pro-inflammatory T cells to the heart and increased T cell expansion in the lymph nodes that connect with the heart. This means that targeting early macrophage infiltration may be a viable approach to treating heart failure.

Finally, the researchers suggest that the increased numbers of circulating monocytes could also potentially be a useful biomarker that indicates an increase of CCR2+ macrophages in the cardiac tissue. This could also help guide patient selection for clinical trials.

Conclusion



The modulation of immune cells and the resulting immune response have been the focus of a number of recent studies for a variety of diseases, and this technique holds a great deal of promise. Now that we know that blood monocyte-derived macrophages infiltrating the heart shortly after pressure overload are a key step in the development of heart failure, we have a new target for therapies that suppress the early infiltration of macrophages and could potentially prevent heart failure.

Literature

[1] Patel, B., Bansal, S. S., Ismahil, M. A., Hamid, T., Rokosh, G., Mack, M., & Prabhu, S. D. (2018). CCR2+ Monocyte-Derived Infiltrating Macrophages Are Required for Adverse Cardiac Remodeling During Pressure Overload. JACC: Basic to Translational Science.

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About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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