Researchers at the NYU Langone Medical Center have just discovered one of the main causes of atherosclerosis – the buildup of fatty materials in an artery causing it to be narrowed. The study, which was published online by Nature Immunology, explains how macrophages, disease-causing cells that accumulate in arteries, contribute to the development of the disease.

The senior author of the study, Kathryn J. Moore, PhD, said

“We have discovered that macrophages that accumulate in plaques secrete a molecule called netrin-1. Our study shows that netrin-1 blocks the normal migration of macrophages out of arteries, causing these immune cells to accumulate and promote the progression of atherosclerosis.”

Macrophages are sent to arteries by the immune system to clean up cholesterol pockets, however, when they are filled with the detrimental form of cholesterol they get trapped and provoke an inflammatory response. The swelled macrophages then become a component of the plaque found in the artery walls. Before, it had been unknown why macrophages were found so abundantly in artery plaques.

The cells remain stuck in the artery plaque leading to Atherosclerosis. The netrin-1 secretion prevents the macrophages from leaving the artery as it signals the cells to stop any form of migration. Experiments show that genetically eliminating netrin-1 results in a reduction of macrophages in artery plaque and minimization of atherosclerosis.

The study at the Langone Medical Center involved monitoring the movement of macrophage cells in and out of plaques using a florescent tracking technique. They found that the macrophages that were in the presence of netrin-1 were immobilized in the plaque and accumulated in number, but the ones where netrin-1 had been deleted were able to emigrate from the plaque.

Lead author of the study and post-doctoral researcher in the Marc and Ruti Bell Vascular Biology and Disease Program, Janine M. van Gils, PhD, said the following

“Our study identifies netrin-1 as a novel target for future therapeutic intervention for the treatment of atherosclerosis and cardiovascular disease. This discovery provides new clues to help reduce the amount of plaque in arteries and the threat of atherosclerosis, a major cause of mortality in Western countries. The development of a new strategy to diminish macrophage accumulation in plaque offers great promise to reducing the occurrence of fatal cardiac events.”

Written by Joseph Nordqvist