Particular Bone Marrow Factors Linked to Heart Disease

Illustration of red blood cells moving through clogged Artery
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Researchers at Massachusetts General Hospital (MGH) recently studied aspects related to the production of white blood cells. Their findings may pave a way for new therapeutics and strategies to protect cardiovascular health.

Their work is published in the journal Nature Cardiovascular Research, in a paper titled, “Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease.”

“Abnormal hematopoiesis advances cardiovascular disease by generating excess inflammatory leukocytes that attack the arteries and the heart,” the researchers wrote. “The bone marrow niche regulates hematopoietic stem cell proliferation and hence the systemic leukocyte pool, but whether cardiovascular disease affects the hematopoietic organ’s microvasculature is unknown. Here we show that hypertension, atherosclerosis, and myocardial infarction (MI) instigate endothelial dysfunction, leakage, vascular fibrosis, and angiogenesis in the bone marrow, altogether leading to overproduction of inflammatory myeloid cells and systemic leukocytosis.”

“In patients with heart disease, white blood cells are more numerous,” said senior author Matthias Nahrendorf, M.D., Ph.D., an investigator in MGH’s Center for Systems Biology and a professor of radiology at Harvard Medical School. “Many of these cells can be found in plaque—the buildup of fats, cholesterol, and other substances in a blood vessel—where they arrive after being born in the bone marrow and migrating through the bloodstream. But what leads to their increased bone marrow output is not clear.”

The researchers conducted their studies in human bone marrow and in mice, and discovered that high blood pressure, atherosclerosis, and the occurrence of a heart attack each can cause changes in the number of blood vessels in the bone marrow.

“As a consequence, more white blood cells were available in the body, and this increase, called leukocytosis, propels inflammation everywhere, including in the arteries and the heart,” explained Nahrendorf. “This study will allow us to now examine how to reduce white blood cell production to normal values, thereby cooling off inflamed plaques anywhere in the body.”

The findings demonstrate that cardiovascular disease affects the bone marrow vasculature and consequently blood stem cell activity.

“This work sheds new light on the important role played by the vascular bone marrow niche and how inflammation occurs,” explained Michelle Olive, PhD, program officer in the division of cardiovascular sciences at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. “It could lead to new targets and treatments for heart disease, the leading cause of death.”

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