Bioimaging analysis of a mouse model of atherosclerosis using radioisotope-labeled oxidized LDL as a probe targeting on foamy macrophages

Abstract

Atherosclerotic plaques are formed by the accumulation of foamy macrophages, which phagocytose oxidized low-density lipoprotein (LDL) in the intima of blood vessels. Although bioimaging to detect the accumulation of foamy macrophages is thought to be an effective tool for the prevention and treatment of atherosclerosis, it has not yet been established. In this study, we examined the bioimaging of atherosclerotic plaques using human oxidized LDL (oxLDL) labeled with ¹²⁵I in apolipoprotein E knockout (ApoE-KO) mice, a mouse model of atherosclerosis. Mouse bone marrow-derived macrophages markedly phagocytosed oxLDL but not intact LDL (LDL). The Oil Red O staining revealed that massive amounts of atherosclerosis plaques were formed in the aortic arch and aortic valve in ApoE-KO mice. In the study of single photon emission computed tomography (SPECT), distinct signals were detected in the aorta of ApoE-KO mice treated with ¹²⁵I-labeled oxLDL but not with ¹²⁵I-labeled LDL. The local distribution of radioactivity was also detected by autoradiography. We further confirmed the uptake of DiI-labeled oxLDL by macrophages accumulated in atherosclerotic plaques in ApoE-KO mice. A possibility is suggested that bioimaging for the diagnosis of atherosclerosis could be developed with the strategies such as application of radioisotope-labeled oxLDL.