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

© 2018 American Heart Association, Inc..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:38

Enthalten in:

Arteriosclerosis, thrombosis, and vascular biology - 38(2018), 5 vom: 01. Mai, Seite 1030-1036

Sprache:

Englisch

Beteiligte Personen:

Li, Wenjun [VerfasserIn]
Luehmann, Hannah P [VerfasserIn]
Hsiao, Hsi-Min [VerfasserIn]
Tanaka, Satona [VerfasserIn]
Higashikubo, Ryuji [VerfasserIn]
Gauthier, Jason M [VerfasserIn]
Sultan, Deborah [VerfasserIn]
Lavine, Kory J [VerfasserIn]
Brody, Steven L [VerfasserIn]
Gelman, Andrew E [VerfasserIn]
Gropler, Robert J [VerfasserIn]
Liu, Yongjian [VerfasserIn]
Kreisel, Daniel [VerfasserIn]

Links:

Volltext

Themen:

147336-22-9
Animals
Atherosclerosis
CX3C Chemokine Receptor 1
Ccr2 protein, mouse
Cx3cr1 protein, mouse
Green Fluorescent Proteins
Journal Article
Luminescent Proteins
Mice
Positron emission tomography
Receptors, CCR2
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Video-Audio Media

Anmerkungen:

Date Completed 08.07.2019

Date Revised 13.12.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1161/ATVBAHA.117.310517

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM282231684