Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by Intravital 2-Photon and Positron Emission Tomography–Based Imaging—Brief Report

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 38; no. 5; pp. 1030 - 1036
• Main Authors: Li, Wenjun, Luehmann, Hannah P, Hsiao, Hsi-Min, Tanaka, Satona, Higashikubo, Ryuji, Gauthier, Jason M, Sultan, Deborah, Lavine, Kory J, Brody, Steven L, Gelman, Andrew E, Gropler, Robert J, Liu, Yongjian, Kreisel, Daniel
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.05.2018
• Subjects: Animals; Aorta, Thoracic - diagnostic imaging; Aorta, Thoracic - metabolism; Aorta, Thoracic - pathology; Aorta, Thoracic - transplantation; Aortic Diseases - diagnostic imaging; Aortic Diseases - genetics; Aortic Diseases - metabolism; Aortic Diseases - pathology; Atherosclerosis - diagnostic imaging; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; CX3C Chemokine Receptor 1 - genetics; Disease Models, Animal; Female; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Intravital Microscopy - methods; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Macrophages - metabolism; Macrophages - pathology; Male; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout, ApoE; Microscopy, Fluorescence, Multiphoton; Monocytes - metabolism; Monocytes - pathology; Plaque, Atherosclerotic; Positron Emission Tomography Computed Tomography; Receptors, CCR2 - metabolism; Red Fluorescent Protein; Time Factors; atherosclerosis; animals; positron emission tomography; mice
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.117.310517

OBJECTIVE—Aortic arch transplants have advanced our understanding of processes that contribute to progression and regression of atherosclerotic plaques. To characterize the dynamic behavior of monocytes and macrophages in atherosclerotic plaques over time, we developed a new model of cervical aortic arch transplantation in mice that is amenable to intravital imaging. APPROACH AND RESULTS—Vascularized aortic arch grafts were transplanted heterotropically to the right carotid arteries of recipient mice using microsurgical suture techniques. To image immune cells in atherosclerotic lesions during regression, plaque-bearing aortic arch grafts from B6 ApoE-deficient donors were transplanted into syngeneic CX3CR1 GFP reporter mice. Grafts were evaluated histologically, and monocytic cells in atherosclerotic plaques in ApoE-deficient grafts were imaged intravitally by 2-photon microscopy in serial fashion. In complementary experiments, CCR2 cells in plaques were serially imaged by positron emission tomography using specific molecular probes. Plaques in ApoE-deficient grafts underwent regression after transplantation into normolipidemic hosts. Intravital imaging revealed clusters of largely immotile CX3CR1 monocytes/macrophages in regressing plaques that had been recruited from the periphery. We observed a progressive decrease in CX3CR1 monocytic cells in regressing plaques and a decrease in CCR2 positron emission tomography signal during 4 months. CONCLUSIONS—Cervical transplantation of atherosclerotic mouse aortic arches represents a novel experimental tool to investigate cellular mechanisms that contribute to the remodeling of atherosclerotic plaques.