Foamy monocytes have recently emerged as a biomarker for measuring cardiovascular disease risk and a drug target for preventing plaque formation. However, it is unclear how these cells become activated in blood and then accumulate in the arterial vessel wall. Now, a new article published in the Journal of Immunology unveils a mechanism through which foamy monocytes stick to the inside of arteries and form plaque. Doctoral research conducted by Greg Foster and his colleagues in Scott Simon’s lab demonstrates that integrins CD11c and very late antigen-4 (VLA-4) are in an activated state on the surface of foamy monocytes. These activated integrins bind vascular cell adhesion molecule-1 (VCAM-1) expressed on the surface of endothelial cells at the atheroprone regions of the vasculature. Bonds between the integrins and VCAM-1 support shear resistant capture of foamy monocytes in blood and contribute to atherosclerosis.

Microfluidic device that simulates fluid flow in the coronary arteries developed by the Simon Lab. Photo credit: Greg Foster

In order to characterize the role of CD11c and VLA-4 during foamy monocyte recruitment, the Simon Lab developed a unique artery on a chip (A-Chip) microfluidic device, which simulates fluid flow in the coronary arteries. A small drop of blood (obtained from mice or humans fed a high fat meal) is sheared over a glass substrate presenting VCAM-1 and capture of foamy monocytes is imaged in real time using a fluorescence microscope. With this tool, Foster found that activation of CD11c initiates an intracellular signaling event that leads to activation of VLA-4. Furthermore, he found that blocking the activation of CD11c abrogated foamy monocyte recruitment. This data suggests that CD11c is a potential target for ameliorating the recruitment of foamy monocytes and preventing atherosclerosis.

Activation of CD11c initiates an intracellular signaling event that leads to activation of VLA-4. Blocking the activation of CD11c abrogated foamy monocyte recruitment. Credit: Greg Foster