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.
Highlights
Despite considerable therapeutic advances over the past 50 years, atherosclerosis-related cardiovascular diseases (CVD) remain the leading cause of death worldwide[1]
These results demonstrate that the infrared fluorescent protein (iRFP) TG macrophages display a bright iRFP signal and that the fluorescence intensity increased in a cell number-dependent manner
We showed here that endogenous iRFP fluorescence as a sensitive marker for imaging deep tissue pathologies, such as aortic atherosclerotic lesions
Summary
Despite considerable therapeutic advances over the past 50 years, atherosclerosis-related cardiovascular diseases (CVD) remain the leading cause of death worldwide[1]. IRFP is brighter, stronger and more stable than previous generations of similar fluorescent proteins[12] These qualities make iRFP useful for in vivo imaging with great deep tissue penetration and minimal autofluorescence. We established a noninvasive, in vivo atherosclerosis imaging system using iRFP hematopoietic cell-transplanted LDLR−/− mice To our knowledge, this is the first reported use of the endogenous iRFP fluorescence expression to image atherosclerotic lesions from 0 to 8 weeks without an invasive method or injection of imaging reagents. This is the first reported use of the endogenous iRFP fluorescence expression to image atherosclerotic lesions from 0 to 8 weeks without an invasive method or injection of imaging reagents We believe that this novel noninvasive imaging approach will prove to be very helpful for monitoring disease progression in drug intervention studies with animal models
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