Mounting evidence from basic research over the past decade reveals that inflammation and endothelial dysfunction are the central processes in all stages of atherosclerosis; determining levels of the inflammatory mediators (cells such macrophages, or enzymes such as matrix metalloproteinase) accumulated in the plaque would be a way to estimate vulnerability. We have modified human low density lipoprotein (isolated from donor blood) and turned them into nanoparticles carrying a GdDPTA contrast agent. MRI can visualize their uptake by the macrophages in the atheroplaque of apoE-/- mice.
We also developed high-density lipoprotein (HDL)-like nanoparticle that contains iron oxide clusters whose uptake in the atheroplaque is confirmed by Prussian blue staining.
Arteriolosclerosis in LDLr-/- mouse detected by in vivo (A-B) and ex vivo (C) MR imaging. Diagram of lipoprotein-iron oxide (IO) nonoparticles (D) and Prussian blue staining of artery segments after injection ofnanoparticles (E). AA= ascending aorta, DA= descending aorta.