A new study has found that bone marrow factors lead to increased production of white blood cells that drive inflammation in cardiovascular disease.

The research has been published in the Nature Cardiovascular Research Journal. "In patients with heart disease, white blood cells are more numerous," said senior author Matthias Nahrendorf, MD, PhD, 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 a 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," Nahrendorf added.

Through experiments conducted in human bone marrow and mice, Nahrendorf and his colleagues found 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. These hallmarks of cardiovascular disease also changed the bone marrow vessels' structure and function and affected their release of factors that regulate white blood cell production and migration.

"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," Nahrendorf added. Co-authors include MGH's David Rohde, MD, Katrien Vandoorne, PhD and others.

"This study provides strong evidence that cardiovascular disease affects the bone marrow vasculature and consequently blood stem cell activity," said 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.

"This work sheds new light on the important role played by the vascular bone marrow niche and how inflammation occurs. It could lead to new targets and treatments for heart disease, the leading cause of death," she concluded.