A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System
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-...
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| Published in: | Scientific reports Vol. 8; no. 1; pp. 14515 - 11 |
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| Main Authors: | , , , , , , , , , , , , |
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28-09-2018
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| 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. |
|---|---|
| AbstractList | 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. 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. 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. 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. |
| ArticleNumber | 14515 |
| Author | Hiraishi, Yukiko Takahashi, Satoru Sakaguchi, Shota Sakasai, Tomoki Tran, Mai Thi Nhu Fleischmann, Bernd K. Sugiyama, Yuka Kulathunga, Kaushalya Tanaka, Junko Miwa, Yoshihiro Cheng, Olivia Hamada, Michito Otake, Mao |
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| CitedBy_id | crossref_primary_10_3389_fphar_2019_00766 crossref_primary_10_1038_s41467_023_36582_1 crossref_primary_10_1016_j_celrep_2022_110845 crossref_primary_10_1038_s41598_023_48562_y |
| Cites_doi | 10.1016/j.jacc.2005.03.074 10.1016/j.ejphar.2017.05.010 10.1161/01.CIR.0000105761.00573.50 10.1038/nrd1007 10.1038/nature06803 10.1038/nri3520 10.1056/NEJM199901143400207 10.1161/01.CIR.92.3.657 10.1016/j.cell.2011.04.005 10.1038/nri2415 10.1136/heart.89.10.1262 10.1038/nm1102-1235 10.1038/srep21785 10.1538/expanim.63.311 10.1038/nbt.1918 10.1016/j.cmet.2005.02.002 10.1161/01.CIR.0000017860.20619.23 10.1161/CIRCRESAHA.113.302813 10.1038/nm.3258 10.1016/j.jcmg.2017.11.030 10.1038/srep22608 10.1038/s41467-017-00138-x 10.1038/nrcardio.2009.228 10.1016/j.jcmg.2012.07.007 10.1016/j.cytogfr.2015.04.003 10.1038/86684 10.1172/JCI117179 |
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| Keywords | In Vivo Imaging System (IVIS) Plaque Macrophages Near-infrared Fluorescent Protein IVIS Images Atherosclerosis Induction |
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| Snippet | By using near-infrared fluorescent protein (iRFP)-expressing hematopoietic cells, we established a novel, quantitative,
in vivo
, noninvasive atherosclerosis... By using near-infrared fluorescent protein (iRFP)-expressing hematopoietic cells, we established a novel, quantitative, in vivo, noninvasive atherosclerosis... Abstract By using near-infrared fluorescent protein (iRFP)-expressing hematopoietic cells, we established a novel, quantitative, in vivo, noninvasive... |
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| SubjectTerms | 14/35 631/1647/245/2225 631/61/17/1511 64/110 64/60 Actin Actins - genetics Animals Aorta Aortic Diseases - diagnostic imaging Aortic Diseases - genetics Arteriosclerosis Atherosclerosis Atherosclerosis - diagnostic imaging Atherosclerosis - etiology Atherosclerosis - genetics Atherosclerosis Induction Azo Compounds Bone marrow Bone Marrow Transplantation Cholesterol Cholesterol, Dietary - toxicity Coloring Agents Coronary vessels Flow Cytometry Genes, Reporter Genes, Synthetic Humanities and Social Sciences In Vivo Imaging System (IVIS) IVIS Images Low density lipoprotein receptors Luminescent Measurements - methods Luminescent Proteins - analysis Luminescent Proteins - genetics Macrophages Macrophages, Peritoneal - chemistry Macrophages, Peritoneal - ultrastructure Mice Mice, Transgenic Microscopy, Fluorescence multidisciplinary Near-infrared Fluorescent Protein Optical Imaging - methods Plaque Macrophages Plaque, Atherosclerotic - diagnostic imaging Plaques Promoter Regions, Genetic Receptor density Receptors, LDL - deficiency Recombinant Proteins - analysis Recombinant Proteins - genetics Rodents Science Science (multidisciplinary) Thorax |
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| Title | A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System |
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