Wenjun Li1, Hannah P Luehmann2, Hsi-Min Hsiao1, Satona Tanaka1, Ryuji Higashikubo1, Jason M Gauthier1, Deborah Sultan2, Kory J Lavine3, Steven L Brody3, Andrew E Gelman1,4, Robert J Gropler2, Yongjian Liu5, Daniel Kreisel6,4. 1. From the Department of Surgery (W.L., H.-M.H., S.T., R.H., J.M.G., A.E.G., D.K.). 2. Department of Radiology (H.P.L., D.S., R.J.G., Y.L.). 3. Department of Medicine (K.J.L., S.L.B.). 4. Department of Pathology and Immunology (A.E.G., D.K.), Washington University in St. Louis, MO. 5. Department of Radiology (H.P.L., D.S., R.J.G., Y.L.) kreiseld@wustl.edu yongjianliu@wustl.edu. 6. From the Department of Surgery (W.L., H.-M.H., S.T., R.H., J.M.G., A.E.G., D.K.) kreiseld@wustl.edu yongjianliu@wustl.edu.
Abstract
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.
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 atheroscleroticmouse aortic arches represents a novel experimental tool to investigate cellular mechanisms that contribute to the remodeling of atherosclerotic plaques.
Authors: Peggy Robinet; Dianna M Milewicz; Lisa A Cassis; Nicholas J Leeper; Hong S Lu; Jonathan D Smith Journal: Arterioscler Thromb Vasc Biol Date: 2018-01-04 Impact factor: 8.311
Authors: Alan Daugherty; Alan R Tall; Mat J A P Daemen; Erling Falk; Edward A Fisher; Guillermo García-Cardeña; Aldons J Lusis; A Phillip Owens; Michael E Rosenfeld; Renu Virmani Journal: Arterioscler Thromb Vasc Biol Date: 2017-07-20 Impact factor: 8.311
Authors: Catherine Martel; Wenjun Li; Brian Fulp; Andrew M Platt; Emmanuel L Gautier; Marit Westerterp; Robert Bittman; Alan R Tall; Shu-Hsia Chen; Michael J Thomas; Daniel Kreisel; Melody A Swartz; Mary G Sorci-Thomas; Gwendalyn J Randolph Journal: J Clin Invest Date: 2013-03-25 Impact factor: 14.808
Authors: Eugene Trogan; Jonathan E Feig; Snjezana Dogan; George H Rothblat; Véronique Angeli; Frank Tacke; Gwendalyn J Randolph; Edward A Fisher Journal: Proc Natl Acad Sci U S A Date: 2006-03-01 Impact factor: 11.205
Authors: Daniela Dal-Secco; Jing Wang; Zhutian Zeng; Elzbieta Kolaczkowska; Connie H Y Wong; Björn Petri; Richard M Ransohoff; Israel F Charo; Craig N Jenne; Paul Kubes Journal: J Exp Med Date: 2015-03-23 Impact factor: 14.307
Authors: Hong S Lu; Ann Marie Schmidt; Robert A Hegele; Nigel Mackman; Daniel J Rader; Christian Weber; Alan Daugherty Journal: Arterioscler Thromb Vasc Biol Date: 2019-12-23 Impact factor: 8.311