Atherosclerosis is a disease in which fatty substances build-up within an artery, creating a plaque. Inflammatory processes, in particular monocyte and macrophage supply and recruitment, are key to the development of atherosclerosis, which over time can harden the arteries, restricting blood flow and oxygen supply to vital organs and increasing the risk of serious complications of cardiovascular disease such as strokes and heart attacks.
During the study Claudia Monaco, lead author, found that CD200 deficiency led to increased monopoiesis and an accumulation of monocytes and macrophages during atherogenesis, leading to worse atherosclerosis. However, by administrating a CD200-Fusion protein to activate the pathway, the team found that neointima formation, was reduced.
“Both systemic and local components of the immune system are important in atherogenesis, and CD200 can regulate both systemic and local inflammatory factors by acting within the artery wall but also on monopoiesis in the bone marrow,” said Claudia.
CD200 controls macrophage activation by interacting with the inhibitory receptor CD200R. The CD200 - CD200R pathway was shown to restrain activation of CD200R+ lesional macrophages, their production of CCR2 ligands, and monocyte recruitment in vitro and in vivo in an air pouch model.
Bone marrow chimera experiments performed by the team revealed that the CD200 – CD200R pathway enables two complementary and tissue dependent strategies to limit atherogenesis. “CD200 expression by bone-marrow derived cells limits systemic monocytosis, while CD200 expression by non-haematopoietic cells, for example endothelial cells, prevents local plaque growth,” said Claudia.
This is the first study to reveal a role for the CD200/CD200R pathway in atherosclerosis and it makes it a possible target for finding a potential therapeutic pathway to treat cardiovascular disease. This research was supported by the British Heart Foundation, The European Commission, the Kennedy trustees and the Novo Nordisk Foundation.
The research is explained in Nature Reviews Cardiology.