Date: 31st January 2020
Atherosclerosis is a condition where the arteries become narrowed and hardened due to an accumulation of plaque around the artery wall. It is the primary cause of coronary heart disease (CHD), which occurs when the arteries that carry blood to the heart muscle are affected and is the leading cause of death worldwide, killing over 7 million people per year. Now scientists have turned to the immune system and nanotechnology – creating ‘Trojan horse’ nanoparticles to prevent atherosclerotic cardiovascular disease.
The team of scientists from Michigan State University and Stanford University were led by Nicholas Leeper and Bryan Smith and published their findings in Nature Nanotechnology.
Leeper and colleagues had previously started to unravel why plaques, and as it turns out cancer cells, remain ‘stealthy’ to the immune system. One finding is that these cells often upregulate CD47, a key anti-phagocytic molecule which is recognised by signal-regulatory protein alpha (SIRPα), the main receptor of CD47 expressed by macrophages. Once bound, these molecules deliver ‘don’t eat me’ signals to the macrophages, preventing them from activating.
A feature of the atherosclerotic plaque is the accumulation of apoptotic cells in the necrotic core. Leeper and others have made efforts to utilise this characteristic by stimulating phagocytic clearance of these cells, thereby reducing plaque size. However, these antibody-based therapies, such as CD47-blocking antibody, often caused off-target clearance of healthy tissues, leading to toxicities such as anaemia.
To build on this previous work, the team asked how they could they block this cloaking ‘don’t eat me’ signal, and so reactivate the macrophages to seek out and destroy the plaques in a more specific approach.
Flores, A. M., N. Hosseini-Nassab, K.-U. Jarr, J. Ye, X. Zhu, R. Wirka, A. L. Koh, P. Tsantilas, Y. Wang, V. Nanda, Y. Kojima, Y. Zeng, M. Lotfi, R. Sinclair, I. L. Weissman, E. Ingelsson, B. R. Smith and N. J. Leeper (2020). “Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis.” Nature Nanotechnology.