1. A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System
- Author
-
Yukiko Hiraishi, Mai Thi Nhu Tran, Bernd K. Fleischmann, Satoru Takahashi, Yoshihiro Miwa, Michito Hamada, Mao Otake, Tomoki Sakasai, Kaushalya Kulathunga, Olivia Cheng, Junko Tanaka, Yuka Sugiyama, and Shota Sakaguchi
- Subjects
0301 basic medicine ,Pathology ,030204 cardiovascular system & hematology ,Cholesterol, Dietary ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Genes, Reporter ,Genes, Synthetic ,Thoracic aorta ,Near-infrared Fluorescent Protein ,Coloring Agents ,Promoter Regions, Genetic ,In Vivo Imaging System (IVIS) ,Bone Marrow Transplantation ,Multidisciplinary ,Optical Imaging ,Flow Cytometry ,Plaque, Atherosclerotic ,Recombinant Proteins ,medicine.anatomical_structure ,Medicine ,Preclinical imaging ,medicine.medical_specialty ,Normal diet ,Science ,Aortic Diseases ,Mice, Transgenic ,Article ,03 medical and health sciences ,In vivo ,medicine.artery ,medicine ,Animals ,Oil Red O ,Atherosclerosis Induction ,Aorta ,Atherosclerosis ,Plaque Macrophages ,Actins ,Luminescent Proteins ,030104 developmental biology ,Microscopy, Fluorescence ,Receptors, LDL ,chemistry ,Luminescent Measurements ,Macrophages, Peritoneal ,Bone marrow ,Azo Compounds ,IVIS Images ,Lipoprotein - 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.
- Published
- 2018