A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System

Abstract By using near-infrared fluorescent protein (iRFP)-expressing hematopoietic cells, we established a novel, quantitative, in vivo, noninvasive atherosclerosis imaging system. This murine atherosclerosis imaging approach targets macrophages expressing iRFP in plaques. Low-density lipoprotein r...

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Autores principales: Kaushalya Kulathunga, Michito Hamada, Yukiko Hiraishi, Mao Otake, Mai Thi Nhu Tran, Olivia Cheng, Junko Tanaka, Tomoki Sakasai, Shota Sakaguchi, Yuka Sugiyama, Bernd K. Fleischmann, Satoru Takahashi, Yoshihiro Miwa
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/4d61aeb86c6e4b90a0b29fc94a27c589
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spelling oai:doaj.org-article:4d61aeb86c6e4b90a0b29fc94a27c5892021-12-02T11:40:46ZA Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System10.1038/s41598-018-32456-52045-2322https://doaj.org/article/4d61aeb86c6e4b90a0b29fc94a27c5892018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32456-5https://doaj.org/toc/2045-2322Abstract By using near-infrared fluorescent protein (iRFP)-expressing hematopoietic cells, we established a novel, quantitative, in vivo, noninvasive atherosclerosis imaging system. This murine atherosclerosis imaging approach targets macrophages expressing iRFP in plaques. Low-density lipoprotein receptor-deficient (LDLR −/− ) mice transplanted with beta-actin promoter-derived iRFP transgenic (TG) mouse bone marrow (BM) cells (iRFP → LDLR −/− ) were used. Atherosclerosis was induced by a nonfluorescent 1.25% cholesterol diet (HCD). Atherosclerosis was compared among the three differently induced mouse groups. iRFP → LDLR −/− mice fed a normal diet (ND) and LDLR −/− mice transplanted with wild-type (WT) BM cells were used as controls. The in vivo imaging system (IVIS) detected an enhanced iRFP signal in the thoracic aorta of HCD-fed iRFP → LDLR −/− mice, whereas iRFP signals were not observed in the control mice. Time-course imaging showed a gradual increase in the signal area, which was correlated with atherosclerotic plaque progression. Oil red O (ORO) staining of aortas and histological analysis of plaques confirmed that the detected signal was strictly emitted from plaque-positive areas of the aorta. Our new murine atherosclerosis imaging system can noninvasively image atherosclerotic plaques in the aorta and generate longitudinal data, validating the ability of the system to monitor lesion progression.Kaushalya KulathungaMichito HamadaYukiko HiraishiMao OtakeMai Thi Nhu TranOlivia ChengJunko TanakaTomoki SakasaiShota SakaguchiYuka SugiyamaBernd K. FleischmannSatoru TakahashiYoshihiro MiwaNature PortfolioarticleIn Vivo Imaging System (IVIS)Near-infrared Fluorescent ProteinIVIS ImagesPlaque MacrophagesAtherosclerosis InductionMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution DOAJ
collection DOAJ
language EN
topic In Vivo Imaging System (IVIS)
Near-infrared Fluorescent Protein
IVIS Images
Plaque Macrophages
Atherosclerosis Induction
Medicine
R
Science
Q
spellingShingle In Vivo Imaging System (IVIS)
Near-infrared Fluorescent Protein
IVIS Images
Plaque Macrophages
Atherosclerosis Induction
Medicine
R
Science
Q
Kaushalya Kulathunga
Michito Hamada
Yukiko Hiraishi
Mao Otake
Mai Thi Nhu Tran
Olivia Cheng
Junko Tanaka
Tomoki Sakasai
Shota Sakaguchi
Yuka Sugiyama
Bernd K. Fleischmann
Satoru Takahashi
Yoshihiro Miwa
A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System
description Abstract By using near-infrared fluorescent protein (iRFP)-expressing hematopoietic cells, we established a novel, quantitative, in vivo, noninvasive atherosclerosis imaging system. This murine atherosclerosis imaging approach targets macrophages expressing iRFP in plaques. Low-density lipoprotein receptor-deficient (LDLR −/− ) mice transplanted with beta-actin promoter-derived iRFP transgenic (TG) mouse bone marrow (BM) cells (iRFP → LDLR −/− ) were used. Atherosclerosis was induced by a nonfluorescent 1.25% cholesterol diet (HCD). Atherosclerosis was compared among the three differently induced mouse groups. iRFP → LDLR −/− mice fed a normal diet (ND) and LDLR −/− mice transplanted with wild-type (WT) BM cells were used as controls. The in vivo imaging system (IVIS) detected an enhanced iRFP signal in the thoracic aorta of HCD-fed iRFP → LDLR −/− mice, whereas iRFP signals were not observed in the control mice. Time-course imaging showed a gradual increase in the signal area, which was correlated with atherosclerotic plaque progression. Oil red O (ORO) staining of aortas and histological analysis of plaques confirmed that the detected signal was strictly emitted from plaque-positive areas of the aorta. Our new murine atherosclerosis imaging system can noninvasively image atherosclerotic plaques in the aorta and generate longitudinal data, validating the ability of the system to monitor lesion progression.
format article
author Kaushalya Kulathunga
Michito Hamada
Yukiko Hiraishi
Mao Otake
Mai Thi Nhu Tran
Olivia Cheng
Junko Tanaka
Tomoki Sakasai
Shota Sakaguchi
Yuka Sugiyama
Bernd K. Fleischmann
Satoru Takahashi
Yoshihiro Miwa
author_facet Kaushalya Kulathunga
Michito Hamada
Yukiko Hiraishi
Mao Otake
Mai Thi Nhu Tran
Olivia Cheng
Junko Tanaka
Tomoki Sakasai
Shota Sakaguchi
Yuka Sugiyama
Bernd K. Fleischmann
Satoru Takahashi
Yoshihiro Miwa
author_sort Kaushalya Kulathunga
title A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System
title_short A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System
title_full A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System
title_fullStr A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System
title_full_unstemmed A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System
title_sort novel irfp-incorporated in vivo murine atherosclerosis imaging system
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/4d61aeb86c6e4b90a0b29fc94a27c589
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