The concept of heart failure traditionally referred to a loss of the organ's pumping capacity, which is called systolic heart failure. But in HFpEF the heart retains the ability to pump or eject blood into the circulation. What is compromised is the ability of the heart muscle to relax and allow blood to flow into the left ventricle, reducing the amount of blood available to pump into the aorta. Symptoms of HFpEF are similar to those of heart failure in general, but since factors contributing to the condition are not well understood, it has been difficult to find promising therapies.
Interactions among cells within the heart -- including macrophages -- are essential to normal cardiac function but can also contribute to problems. For example, after the heart muscle is damaged by a heart attack, macrophages induce the cells called fibroblasts to generate the connective tissues that help reinforce damaged tissue. But excessive fibroblast activation can lead to the distortion and stiffening of tissues, further reducing cardiac function.
"Not only were numbers of inflammatory cardiac macrophages increased in both the mice and in humans with HFpEF, but their characteristics and functions were also different from those in a healthy heart," says Hulsmans. "Through their participation in the remodeling of heart tissue, these macrophages increase the production of extracellular matrix, which reduces diastolic relaxation. Our findings regarding the cell-specific knockout of IL-10 are the first to support the contribution of macrophages to HFpEF."
Senior author Mathias Nahrendorf, MD, PhD , of the Center for Systems Biology, adds, "Heart muscle cells and fibroblasts have been considered the major contributors to HFpEF. Our identification of the central involvement of macrophages should give us a new focus for drug development. And since macrophages naturally take up materials for disposal, inducing them to ingest drugs carried in by nanoparticles could limit their contributions to the development of HFpEF." Nahrendorf is a professor of Radiology at Harvard Medical School.
Revealed by Massachusetts General Hospital.
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